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连续性纯合片段在畜禽基因组研究中的应用

本站小编 Free考研考试/2022-01-01
刘刚, 孙飞舟,, 朱芳贤,, 冯海永, 韩旭全国畜牧总站,北京 100193

Runs of homozygosity and its application on livestock genome study

Gang Liu, Feizhou Sun,, Fangxian Zhu,, Haiyong Feng, Xu HanNational Animal Husbandry Service, Beijing 100193, China

通讯作者: 孙飞舟，博士，研究员，研究方向：畜禽遗传资源保护与应用。E-mail: fzhsun1968@qq.com朱芳贤，高级畜牧师，研究方向：畜禽遗传资源保护与应用。E-mail: 1171277193@qq.com

编委: 任军
收稿日期:2018-10-13修回日期:2019-02-2网络出版日期:2019-04-20
基金资助:禽种质资源保护项目.[2018]45
家养动物平台种质资源项目.2018


Received:2018-10-13Revised:2019-02-2Online:2019-04-20
Fund supported: the Protection Project of Animal Germplasm Resources.[2018]45
the National Infrastructure of Domestic Animal Resources.2018

作者简介 About authors
刘刚,博士,畜牧师,研究方向：畜禽遗传资源保护与应用E-mail:lgang-2004@126.com。







摘要
随着高通量SNP芯片技术的快速发展和测序成本的大幅降低,SNP基因芯片和基因组重测序等技术被广泛地应用于畜禽基因组研究中。在基因组某一段区域内,当一定数量和一定密度的SNPs表现为纯合时,可以判定该区域存在连续性纯合片段(runs of homozygosity, ROH)。目前,连续性纯合片段已经逐渐成为分析畜禽群体近交程度、遗传结构等方面的重要指标之一。但是,ROH计算应用的评价标准还相对匮乏。本文系统介绍了连续性纯合片段的发展历史、原理、鉴定方法以及在畜禽群体结构解析、基因组功能分析和种畜禽品质检测等方面的应用情况,以期为畜禽遗传资源保种区和保种场在遗传多样性等动态监测方面提供参考。
关键词： 高通量测序技术;连续性纯合片段;群体结构;基因组功能;遗传缺陷

Abstract
With the rapid development of high-throughput SNP array and significant reduction of sequencing cost, the techniques of genome-resequencing and SNP chip arrays are widely applied in livestock genomic studies. Long runs of homozygosity (ROH) arose when identical haplotypes were inherited from each parent and thus a long tract of genotypes is homozygous. Nowadays, cumulative studies reported that ROH has progressively served as one of the important indexes to estimate the degree of inbreeding and genetic structure of livestock populations. However, the evaluating criteria of ROH in livestock is still inadequate. In this review, we introduce the history, theory and identification methods of ROH analysis. Meanwhile, we also systematically overview the applications and perspectives of ROH in population genetic structure analysis, genome functional assay, quality investigation and dynamic monitoring of livestock genetic resources.
Keywords：high-throughput sequencing;runs of homozygosity;population structure;genomic function;genetic defect


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本文引用格式
刘刚, 孙飞舟, 朱芳贤, 冯海永, 韩旭. 连续性纯合片段在畜禽基因组研究中的应用[J]. 遗传, 2019, 41(4): 304-317 doi:10.16288/j.yczz.18-287
Gang Liu, Feizhou Sun, Fangxian Zhu, Haiyong Feng, Xu Han. Runs of homozygosity and its application on livestock genome study[J]. Hereditas(Beijing), 2019, 41(4): 304-317 doi:10.16288/j.yczz.18-287


单核苷酸多态性(single nucleotide ploymorhphisms, SNPs)是畜禽基因组中最常见的遗传变异,一般指在畜禽群体中频率大于1%单个核苷酸的变异,包括转换、颠换、缺失和插入。在基因组某一段区域内,当一定数量一定密度的SNPs表现为纯合时,可以判定该区域存在连续性纯合片段(runs of homozygosity, ROH)[1]。大量研究表明,ROH信息在畜禽、植物和人类群体近交程度和监测方面发挥着越来越重要的作用[2,3,4,5,6]。通过鉴别和分析ROH分布和频率等指标,可以深入剖析群体在世代间演变的历程,从而揭示这些群体经过系列变化后基因组中纯合片段的模式[7,8,9],也可以评估群体近交水平和群体中个体间的亲缘关系,进一步分析群体选择压力和交配模式等[10,11,12]。利用SNP基因芯片技术分析基因组中ROH是分析同源遗传关系(identical by descent, IBD)的有效方法[1,13]。通过SNP基因芯片技术对畜禽群体进行分析,可以获得同一群体不同世代动态变化的信息,如监测群体有效含量[14,15]和种公畜间近交系数[16]等。

1999年,Broman和Weber[7]首次发现并分析了人类染色体上长纯合片段,结果表明纯合片段的长短与人类健康相关。Gibson等[1]首次利用高密度SNP基因芯片技术分析了人类染色体上纯合片段的长度、频率和分布情况等,解析了人类基因组中存在ROH的机理[2,15,17]。随着畜禽SNP基因芯片和重测序技术的广泛应用[18,19,20],基于畜禽基因组信息的ROH研究也与日俱增。如Marras等[21]对牛(Bos taurus)基因组ROH频率和分布情况等指标进行了分析;此外,在牛[4,10,21~24]、猪(Sus scrofa)[8,9,25~29]、马(Equus caballus)[30,31,32,33]、绵羊(Ovis aries)[34,35,36,37]、山羊(Capra hircus)[38,39]和鸡(Gallus gallus)[40,41,42]等畜禽群体结构和群体演变历史等研究中也利用了ROH特征信息。

本文主要综述了ROH的原理和方法以及在畜禽群体结构、基因组功能分析和种畜禽品质检测等方面的应用,以期为相关研究提供参考。

1 连续性纯合片段产生的原理

祖先单倍型相同的两个拷贝聚集在一个个体时会产生纯合片段,长单倍型片段来源于最近共同祖先,短单倍型片段来源于亲缘关系较远的共同祖先。由于亲缘关系较远个体基因组位点之间的强连锁不平衡形成了短ROH,不同类型群体可以产生长短不一的ROH发散分布。在远交群体中ROH产生取决于群体有效含量(Ne),在Ne小的群体中存在更多的ROH,而Ne越大的群体会产生较少的ROH。由于混合种群血统来源于两个或者更多亲缘关系较远的群体,因而比它们祖先群体的ROH少。由于近交群体经历了瓶颈效应,尤其在个体间亲缘关系比较远的情况下,会产生数量较多的短ROH。但是,随着世代的交替,群体有效含量会越来越小,同时,由于近期近交事件的发生,从而在群体基因组片段中出现越来越多长短不一的ROH[43]。研究表明,ROH更多地富集在有害突变个体中,而在非有害突变个体中聚集较少;即使有害突变频率低于非有害突变的频率,ROH区域可能是有害突变个体发生突变的重要载体[16]。

2 检测连续性纯合片段的方法

根据不同类型数据的特点,可以制定适合于分析ROH的算法。目前分析方法主要包括观测基因型计数法和基于模型的分析方法。

2.1 观测基因型计数法

基因型计数法是根据设定杂合子最大数量和允许缺失基因型的数量,在基因组上鉴定连续纯合基因型的长片段。常用的软件有PLINK[44]、GERMLINE[45]和cgaTOH[46]等。Howrigan等[47]通过计算机模拟试验检测了已知120 Mb人基因组中纯合片段情况,其模拟结果表明,PLINK软件检测个体同一性的性能要优于GERMLINE软件。

2.2 基于模型的分析方法

基于模型的分析方法主要利用隐马尔可夫模型,分辨纯合子和杂合子基因组区域,获得等位基因频率和重组率等参数。常用的软件有BEAGLE[48]、H3M2[49]、FILTUS[50]、BCFtools/RoH[51]和GARLIC[52]等。全基因组重测序深度的增加有利于减少基因型判定的错误率,从而改进隐马尔可夫模型的判定,大大提高检测ROH的精度,进一步确定较短ROH在近交衰退中的作用。

目前,PLINK软件广泛应用于ROH分析中。不同畜禽群体中鉴定ROH不同软件设置参数详见表1。

Table 1
表1
表1 不同畜禽群体中鉴定ROH设置参数比较
Table 1 Comparison of pre-set parameters for identification and characterization of ROH in different animal species
物种 软件/编程语言 每个ROH中
连续SNP数量①		 密度②
(SNP/kb)		 最大间隔③ 最少长度(kb)④ 参考文献
牛
(Bos taurus)		 Fortran 90 15 - - 1000 [4]
PLINK v 1.07 58 1/50 100 500 [10]
PLINK v 1.07 30 - - - [53]
SNP & VARIATION SUITE v 7.6.8 15 1/1000 1000 1000 [5]
SNP & VARIATION SUITE v 7.6.8 50,100 1/50 250 1000 [11]
PLINK v 1.07 - - 1000 - [54]
PLINK v 1.07 50 - - 1000 [55]
SAS 9.2 15 - 1000 1000 [20]
PLINK v1.07 30 - - 1000 [56]
R Development Core team (2018) - 1/50 100 100 [57]
SNP & VARIATION SUITE v 7.6.8 30 1/100 500 4000 [58]
Perl script 50 - - - [59]
PLINK v1.07 50 1/120 1000 500 [60]
PLINK v1.90 50 1/100 1800 3400 [23]
PLINK v1.90 50 1/50 500 1000 [61]
PLINK v1.90 20,35,50 - - - [62]
vcftools - - - 500 [63]
PLINK v1.90 40 1/100 1000 4000 [24]
PLINK v1.90 10 - 1000 - [64]
cgaTOH 58 1/120 1000 500 [65]
SNP & Variation Suite (SVS) 15 1/1000 1000 1000 [66]
PLINK v1.07 20 1/1000 - 10 [8]
PLINK v1.07 - - - 500 [67]
物种 软件/编程语言 每个ROH中
连续SNP数量①		 密度②
(SNP/kb)		 最大间隔③ 最少长度(kb)④ 参考文献
猪
(Sus scrofa)		 PLINK v1.07 20 1/1000 1000 10 [9]
SNP & Variation Suite (SVS) 30 1/100 100 1000 [68]
PLINK v1.07 10 1/500 1000 5000 [23]
Fortran- 30 1/100 1000 - [24]
PLINK v1.09 50 1/50 - 1000 [69]
PLINK v1.09 - - - 500 [25]
PLINK v1.09 40 - - - [70]
PLINK v1.07 50 - - 500 [71]
PLINK v1.07 50 1/100 1000 [72]
PLINK v1.07 - - 250 500 [73]
PLINK v1.07 20 1/50 500 - [33]
绵羊
(Ovis aries)		 SNP & Variation Suite program 25 - 1000 - [74]
PLINK v1.09 - 1/100 250 1000 [34]
PLINK v1.09 - 1/100 1000 1000 [75]
PLINK v1.09 30 1/100 250 1000 [22]
PLINK v1.9 50 - - 500 [76]
PLINK v1.09 50 - - - [77]
In-house script 20 500 2000 [37]
山羊
(Capra hircus)		 PLINK v1.09 25 1/50 1000 1000 [78]
PLINK v1.07 50 1/50 1000 500 [28]
PLINK v1.07 50 - - 400 [29]
马
(Equus caballus)		 PLINK v1.7 1/50 100 500 [30]
PLINK v1.07 100 1/50 100 150 [31]
PLINK v1.9 20 1/50 1000 - [38]
PLINK 1.9 - 1/100 - 1000 [39]
鸡(Gallus gallus) PLINK 1.9 - 1/50 - 100 [40]
①表示一个ROH片段中连续SNP位点数量;②表示在每个运行单元中SNPs的密度;③表示连续纯合子片段之间的最大间隔;④表示鉴定ROH的最小长度。“-”表示无此信息。
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3 连续性纯合片段信息在畜禽基因组研究中的应用

3.1 亲缘关系的鉴定

随着高通量测序技术的迅猛发展,利用基因组信息分析个体和群体间的近交程度越来越被关注,尤其是检测染色体上ROH的长度和分布情况,从而间接地分析群体中个体间的近交程度。通过计算基因组中特定长度(如>1 Mb、>2 Mb、>4 Mb、>8 Mb、>16 Mb等)ROH的值反映群体在基因组水平上的近交程度。

近交系数传统分析方法是假定群体中祖先没有亲缘关系的前提下,通过通径原理分析计算得到的。目前,随着高密度SNP基因芯片技术的广泛应用,在不同畜禽群体中利用基因组信息分析真实的基因组近交程度成为可能。研究表明,基因组信息估测近交程度比传统意义上的系谱信息更有效[4,10,79]。利用系谱信息估测亲缘关系是通过基因组IBD概率的统计期望值,而利用基因组信息估测的是个体间实际的亲缘关系[80,81]。不同畜禽群体中鉴定ROH信息以及基于系谱信息和基因组信息近交系数的相关系数见表2。

Table 2
表2
表2 畜禽群体中鉴定ROH信息以及基于系谱信息和基因组信息近交系数的相关系数统计表
Table 2 Studies of ROH and correlations between the inbreeding from pedigree data and from genome data through ROH in livestock and poultry species
物种 品种/群体 数量 ROH平均
数量		 ROH平均
长度(Mb)		 相关系数 参考文献
FPED①, FROH FPED, FROH>1 Mb FPED, FROH>2 Mb FPED, FROH>4 Mb FPED, FROH>8 Mb FPED, FROH>16 Mb
牛
(Bos taurus)		 Austrian Simmental 500 - - - 0.64 0.67 0.68 0.68 0.63 [4]
Multiple breeds 891 - 0.30~5.09② 0.71 - - - - - [10]
Brown Swiss 304 98.9 1.30 - 0.66 0.67 - 0.60 0.50 [5]
Fleckvieh 502 94.5 0.44 0.66 0.69 0.70 0.64
Nowegian Red 498 80.0 0.51 0.61 0.61 0.62 0.53
Tyrol Grey 117 72.3 1.88 0.71 0.72 0.71 0.70
物种 品种/群体 数量 ROH平均
数量		 ROH平均
长度(Mb)		 相关系数 参考文献
FPED①, FROH FPED, FROH>1 Mb FPED, FROH>2 Mb FPED, FROH>4 Mb FPED, FROH>8 Mb FPED, FROH>16 Mb
牛
(Bos taurus)		 Italian Holstein 2093 81.7 3.6 - 0.70 - 0.69 0.65 0.56 [20]
Italian Brown 749 94.6 3.9 0.66 0.66 0.65 0.58
Italian Simmental 479 94.3 2.2 0.66 0.74 0.76 0.71
Jersey 1602 - - 0.70③/0.71④ - - - - - [57]
Cinisara 71 9.38 13.57 0.45 - - - - - [82]
Modicana 72 110.3 12.31 0.27
Reggiana 168 10.42 10.16 0.31
Italian Holstein 96 7.15 11.78 0.44
Holstein 2107 21.2 8.02 0.73 - - - - - [83]
Maasai - 103 17.46 0.90 - - - - - [84]
Tarime 56 13.12 0.75
Sukuma 36 10.65 0.61
Boran 99 9.48 0.56
Friesian 155 9.68 0.54
Brown Swiss 281 21.0 2264 0.45 - - - - - [23]
Braunvieh 3386 18.6 184.6
Origianl Braunvieh 167 8.4 73.7
Holstein 2568 14.2 145.2
Red Holstein 1960 11.2 112.1
Swiss Fleckvieh 547 7.1 75.6
Simmental 248 10.9 96.6
Eringer 36 8.5 66.2
Evolèner 21 15.5 185.7
猪
(Sus scrofa)		 Iberian 64 - - - 0.77 - - 0.81 - [68]
Yorkshire 2358 - - 0.69 - - - - - [23]
Guadyerbas 109 - - 0.63 -0.24 - - 0.60 - [24]
Landrace 1178 52.7 252.9 0.24 - - - - - [69]
Large White 1200 61.4 280.1 0.015
Duroc 1066 16.72 6.75 0.31 - - - - - [70]
Landrace 768 23.19 11.27 0.32
Yrokshire 1111 25.88 11.99 0.53
Crossbred 112 8.25 2.6 0.00
马
(Equus
caballus)		 Sorraia 2⑤ 4175⑥ 0.19 - - - - - - [29]
Dülmen Horse 1⑤ 2804⑥ 0.14
Arabian 1⑤ 3581⑥ 0.15
Saxon-Thuringian 1⑤ 3138⑥ 0.15
Thoroughbred 1⑤ 4595⑥ 0.20
Hanoverian 4⑤ 311⑥ 0.14
物种 品种/群体 数量 ROH平均
数量		 ROH平均
长度(Mb)		 相关系数 参考文献
FPED①, FROH FPED, FROH>1 Mb FPED, FROH>2 Mb FPED, FROH>4 Mb FPED, FROH>8 Mb FPED, FROH>16 Mb
绵羊
(Ovis aries)		 Belclare 304 39.94~
92.61⑦		 0.83-3.7 - 0.76 - 0.75⑧ 0.71⑨ - [34]
Suffolk 53 0.54 0.55⑧ 0.58⑨
Texel 248 0.52 0.47⑧ 0.41⑨
Vendeen 238 0.15 0.15⑧ 0.12⑨
山羊
(Capra hircus)		 Alpine 403 15.6 0.45 0.372 - - - - - [77]
Boer(Ausralia) 61 23.6 0.48
Boer(Canada) 67 31.5 0.42
Cashmere 48 8.0 0.59
LaMancha 81 19.4 0.47
Nubian 54 31.2 0.43
Rangeland 66 5.2 0.38
Saanen 318 16.7 0.45
Toggenb 53 24.1 0.46
①根据系谱信息计算的近交系数;②估计平均ROH长度为ROH平均覆盖基因组长度与ROH总数量的平均值;③以连续100个纯合子SNPs鉴定为一个ROH;④以连续30、50、80个纯合子SNPs鉴定为一个ROH;⑤序列信息从NCBI获得;⑥使用50 SNPs滑动窗口定义的值;⑦品种间变化范围为39.94~92.61 Mb,每个品种平均ROH变化范围为0.83~3.7 Mb(ROH≥20 Mb);⑧基因组中5 Mb计算的FROH;⑨基因组中10 Mb计算的FROH。“-”表示无此信息。
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目前,基于基因组信息估测近交程度的方法主要有以下3种：(1)基于ROH的近交系数(FROH),是指ROH片段长度之和占整个基因组总长度的比例。McQuillan等[2]引入FROH作为检测个体间同一性指标,其中计算公式中整个基因组是指基因组常染色体上特定区域的长度,不同的研究中设置的具体参数不同;(2)标记基因型中纯合子所占的比例(FHOM),即所检测SNP中的纯合子比例;(3)基于基因组关系矩阵的近交系数(FGRM),其中G矩阵计算方法参考文献[85]。杨湛澄等[83]利用高密度SNP 标记通过两种基因组近交计算方法(FROH和FHOM)分析中国荷斯坦牛基因组近交程度,其结果表明,共检测到44 676个ROH片段,ROH在染色体上并非均匀分布,其长度主要分布在1~10 Mb之间。两种基因组近交系数之间的相关性比较大,而基因组近交系数与系谱近交之间的相关性较低。Peripolli等[61]采用4种近交系数计算方法(FPED、FHOM、FGRM和FROH)对瘤牛群体近交程度进行了评估,结果表明,FROH和FGRM相关性为弱到中度相关;FROH和FHOM相关性从弱到强相关;FPED和FHOM与FGRM和FHOM之间的相关程度为中等;FROH和FPED相关系数随着ROH长度的增加而增大。因此,在群体系谱信息缺失的情况下,FROH可以作为替代方法评价畜禽群体的近交程度。

Keller等[6]研究表明,FROH指标与FPED指标相比,具有以下几方面优点：(1) FROH可以更准确估计共同祖先甚至50代前后代个体基因组中纯合性状态;(2)在系谱信息不完整或者缺失的情况下,FROH指标可以检测基因组中纯合片段分布,同时可以发现与纯合性高的特异性位点;(3) FPED指标是相对于基础群而言的,在基础群假定祖先个体的基因组没有选择和重组事件的发生。此外,减数分裂是一个随机过程,子代获得父母双方遗传物质的过程存在着随机变异,且这样的变异随着减数分裂的增加而增加,而FPED仅是IBD概率的期望值。从表2统计结果看出,在牛和猪品种鉴定ROH研究中,FROH和FPED之间的相关程度为中度或者高度,因此可以仅采用FROH监测牛和猪群体的近交程度。也有研究表明,鉴定ROH的长度与FROH和FPED之间相关程度为正相关(表2),ROH反映了群体过去和现在的亲缘关系,而FPED仅根据现有的系谱记录数据估测近交程度。随着群体系谱信息的不断积累,基于系谱近交系数与基于基因组近交系数的相关性也随之增加[20]。根据Saura等[26]报道,当ROH长度大于5 Mb时,计算的FROH值和FPED值接近,而当ROH长度小于5 Mb时,计算的FROH值比FPED值小4倍多。利用FROH和FPED两种方法估测了和牛群体中个体亲缘关系,其结果表明采用系谱信息数据低估了和牛群体的近交程度,基因组近交系数可以反映真实的近交程度,该结果与已有的研究结果一致[20,24,57]。Metzger等[31]估测了马基因组近交系数,在一个窗口滑动50个SNP条件设置下,FROH值变化范围为0.18~ 0.43。Guangul等[38]估测了5个山羊群体的基因组近交程度,ROH长度从1~16 Mb,其FROH的值从0.0500~0.0048。Brito等[77]采用50K基因芯片通过4种不同的近交系数对9个山羊群体近交程度进行了评估,其中基于系谱和ROH近交系数的相关系数为0.372;基于基因型计数方法和ROH近交系数的相关性高达0.901;而基于ROH和基于VanRaden与基于Leuenegger方法的近交系数均为负相关(相关系数分别为-0.133和-0.264)。Grossi等[70]分析了杜洛克、长白和大约克夏纯种猪以及长白大约克夏猪杂交F1代4个群体共计3057个个体ROH分布情况,其结果表明每个个体ROH平均长度在4个群体中依次为16.72、23.19、25.88和8.25;平均数量分别为6.75 Mb、11.28 Mb、11.99 Mb和2.65 Mb。FPED和FROH相关系数在4个群体中依次为0.31、0.32、0.53和0.00;FEH和FROH相关系数依次为0.41、0.72、0.69和0.64 (表2)。Kim等[63]采用重测序技术对经过选育的126头Hanwoo牛个体进行了检测,通过遗传改良提高了其群体的体重,但是群体的近交程度有所增加,其FROH值比未改良的群体升高了约0.02。通过4种类型近交系数评估瘤牛群体的近交程度,其研究结果表明FPED的值变化范围为0.00~0.327;FROH值变化范围为0.001~0.201。FPED与FROH相关系数和FGRM与FROH相关系数从弱相关变为中等相关,其变化范围从-0.11~0.51;FROH和FROM相关系数从弱相关到强相关;不同长度估测的FROH和FPED相关系数随着ROH长度的增加而增加[61]。通过ROH方法对中国白耳黄鸡、北京油鸡和狼山鸡3个群体的保种效果进行评估,检测到基于系谱的近交系数为0.0789 (白耳黄鸡)~0.2010 (北京油鸡);通过几个世代的保种效果监测,表明其基于系谱的近交系数在其群体中变动幅度比较小,而检测到基于ROH近交系数的值要比基于系谱的值要偏低,其值为0.0511 (白耳黄鸡)~0.0745 (北京油鸡),基于系谱和基于ROH近交系数的相关系数为0.76[25]。综上所述,评估畜禽群体的近交程度,FROH是比较有效的评价指标,可以很好地补充由于系谱信息预测群体近交程度的不足,也可以通过鉴定ROH片段提高IBD片段定位的精度。

3.2 近交衰退的评估

Garrod等[86]发现一些人类疾病,如白血病、尿黑酸尿等,这些遗传疾病在近亲婚姻后代个体中发病率比较高,尤其在近交个体的隐性携带者,通过长纯合子片段可以检测到致病的隐性有害变异。Zhang等[25]发现有害纯合变异体和基因组中ROH片段之间呈现线性相关,致病座位有害基因纯合子出现在ROH上的频率要高于正常基因的频率。Szpiech等[87]研究结果表明,鉴定的ROH高覆盖度片段中包含有较长有害变异区段,这也与引起近交衰退有害基因变异位点一般以纯合子状态存在假设是一致的。Muchadeyi等[35]在南非洲波斯羊3、4和25号染色体上检测到ROH片段上与神经系统、骨骼和大脑发育相关的基因,如LRRTM3基因、DPP6基因和SHH基因。Huson等[88]利用基因组关联分析,结合单倍型分析、选择信号分析和ROH分析共同鉴定了牛20号染色体上SLICK位点。Mészáros等[56]采用ROH和基因组关联分析发现了弗莱维赫牛眼脸内翻遗传缺陷基因组区段。Pryce等[89]基于系谱信息的近交系数估测了奶牛产量和个体健康性状,其研究结果表明群体中近交程度增加1%,一个哺乳期内荷斯坦牛和泽西奶牛奶产量分别减少21 L和12 L。Kim等[63]分析了近50年来美国泽西牛基因组中增加的60多个ROH区域与系谱信息估测的近交增量呈正相关,在3号、7号、8号和12号染色体上鉴定的ROH与后代女儿繁殖率呈负相关,体细胞评分的结果与繁殖性状的结果相似。由于近交衰退引起1号、3号、4号、5号和13号染色体上增加的ROH影响了体细胞评分的结果,染色体上高度纯合性导致繁殖率的下降和乳房炎易感性的增加。Silió等[68]研究了近交衰退对断奶后仔猪生产性能的影响,结果表明由于群体近交系数增加,导致其断奶仔猪生产性能下降,具体表现为近交系数每增加0.1,其日增重减少4.4%,90日龄体重减少1.52%。Saura等[26]分析了伊比利亚猪两个高度近交系中的繁殖性状,近交系数每增加0.1,其仔猪初生后存活率和仔猪出生后总数量有下降的趋势。Feren?akovi?等[5]研究牛群体中ROH分布情况,解析了在群体近交增量增加情况下牛精液品质下降的机理,发现与精子数量相关ROH区域有4个,与精子活力相关ROH区域有5个,但是同时与精子数量和精子活力相关ROH区域仅为1个。

3.3 遗传多样性分析

获得大量畜禽基因组信息使得人们更好地分析畜禽群体遗传多样性等指标。维持群体遗传多样性是畜禽保种的重要任务之一,以便利用更丰富的育种素材获得动物产品。采用基因组信息分析共祖先策略已经应用于保护群体遗传多样性和近交增量的分析中[90]。当保种群体中出现中高近交繁殖的迹象时,基于IBD方法分析共同祖先可以作为一个策略维持遗传多样性和保种计划的适合度[91]。因此,较小的群体有效含量和较高的近交增量会降低群体遗传多样性,通过畜禽保种方案的有效实施,监测群体的遗传变异,防止群体中发生不可逆转遗传多样性的减少,最大限度地增加保种群体适应外部环境变化的能力。Fleming等[40]采用600K基因芯片分析了非洲3个鸡群体的遗传多样性,结果表明,群体中所有染色体仅有16号染色体上没有检测到ROH,每个个体ROH在基因组的覆盖程度为2%~40%。Mastrangelo等[24]为了更好地制定和实施保种计划,分析了30个意大利牛群体遗传多样性,结果表明观测杂合度的值变化范围为0.297~0.358,期望杂合度的值变化范围为0.267~0.353。在祖先群体中群体有效含量较高,但是Pontremolese和Mucca Pisana2个群体有效含量比较低。通过分析个体ROH分布和长度等参数有助于畜禽保种项目的制定和实施,在Pontremolese、Varzese-Ottonese和Mucca Pisana群体中检测到高水平的ROH,如尤其针对这些群体,在实施配种计划中尽量增加种公畜血统,减少其遗传多样性的损失,维持或者增加其群体有效含量。Zhang等[42]采用ROH方法对中国白耳黄鸡、北京油鸡和狼山鸡3个保种群体的遗传多样性、基因组近交系数和纯合性进行分析,经过实施近10年的保种策略,白耳黄鸡和北京油鸡群体的遗传多样性有所下降,狼山鸡群体的遗传多样性有上升的趋势。

3.4 人工选择的追踪

基因组中鉴定的选择信号揭示了驯化群体中双向选择的痕迹。与没有受到人工选择的群体比较,对于优秀种畜禽个体的选育,降低了其群体表型的多样性和重塑了基因组,其中包括基因组中ROH存在的模式[12]。有研究表明,对于选育的优秀种畜禽个体使其基因组中单倍型多样性下降,同时也增加了选择位点相邻位点的纯合性,导致其受到选择区域中的ROH频率增加[11]。ROH并不是随机分布在基因组中,大部分ROH出现在受选择区域。基因组中受选择的区域倾向于产生“ROH岛”,相对于基因组其他区域,这些区域遗传多样性低,纯合性比较高。Purfield等[10]研究了牛基因组中出现ROH频率较高的4条染色体,其中在ROH区域中包含了影响牛免疫力、胴体和难产等重要性状的主效基因。在不同的阿拉伯马群体中也开展了ROH的研究,分析了受到正向选择区域的ROH。Metzger等[31]研究了马基因组中受到选择和未受到选择区域中ROH的功能分布,发现了与细胞代谢、生长发育和免疫系统相关的候选基因。Fleming等[41]采用FST、综合单倍型评分(integrated haplotype score)和ROH等信息检测了在非洲和北非不同生态环境中生长鸡品种的选择信号,分析表明非洲生长的鸡群体选择倾向于热应激和血管生成,而北非群体更倾向于能量平衡,其中鸡品种基因组中2号和3号染色体在不同群体中差异最大。通过长期优秀种畜的选育,群体选择强度增加和有效群体含量减少有可能会导致群体生存力和多样性受到威胁。在畜禽选育和保种过程中,尽量避免群体遗传变异性减少,避免基因组中有害基因的表达。人工选择会导致群体近交系数的增加,因此要采取有效的措施控制近交程度的增加。另外,随着人工授精技术的应用,用于采精的优秀种公牛近交程度也影响着整个配种群体的近交程度[63]。

3.5 功能基因的筛选

Bosse等[8]利用重测序技术和SNP基因芯片技术检测了猪基因组上纯合区域,在欧洲猪品种中发现两个重叠ROH区域,该区域上有与神经系统发育细胞分化相关的11个基因,这些基因在大白猪和利比里亚猪中被验证表达存在差异。在亚洲品种中存在4个共享区域,其中有一个重叠区域仅存在亚洲野猪中,该区域中包括91个基因,并且已经有相关报道表明该区域在亚洲猪品种中经过了正向选择;其中在5号染色体上另一个共享区域包括与氧化还原反应相关的LEMD3和MSRB3基因,与脂肪细胞分化正向调控的WIF1基因。在非洲3个鸡品种中一致的ROH区域内比对发现与脂肪代谢、免疫功能和热激介导相关的基因(FDR<0.15),选择区域内也发现与健康和氧化应激反应相关的基因[38]。通过瘤牛群体中ROH分析,发现群体基因组中有7.01% (175.28 Mb)为纯合区域,在整个群体中鉴定的ROH 14个区域的频率高于50%,发现与泌乳(TRAPPC9)、产奶量和乳成分(IRS2和ANG)、热适应(HSF1、HSPB1和HSPE1)等相关候选基因[61]。Metzger等[31]采用全基因组测序方法分析了英国设得兰群岛上2个微型矮马群体和1个正常体高矮马群体,发现在这2个微型矮马群体和1个正常体高矮马群体中ROH区域内存在4个变异,这4个变异解释了设得兰群岛上矮马群体和其他正常体高马群体中72%体高变异效应。

3.6 种畜禽品质检测

在瑞士Appenzeller Barthuhn鸡群体中存在一种十字鸡喙的遗传缺陷,Joller等[92]在该群体和正常群体中通过检测基因组ROH对存在十字鸡喙个体的遗传机理进行研究,初步假定角蛋白家族基因LOC426217为十字鸡喙遗传缺陷的候选基因,在编码区内发现有两个显著的同义突变,但是十字鸡喙遗传缺陷的遗传机理还有待于进一步研究确认。目前,利用ROH检测种畜禽品质的报道还比较少。通过基因组中ROH信息剖析畜禽遗传缺陷的机制,明确致病基因,采用快速有效的方法进行检测,进一步规范种畜禽市场。我国是畜禽资源大国,据不完全统计,截止2018年12月,我国地方畜禽遗传资源数量为556个,国家级保护区数量为24个,国家级保种场数量为165个。如何利用应用成熟的现代生物技术手段对我国畜禽遗传资源群体进行动态监测,尤其是国家级保种场畜禽群体的动态变化情况,已经成为当前畜禽遗传资源保护领域亟待解决的问题。目前,ROH在不同畜禽基因组中的广泛应用为解决这一难题提供了一定的措施。对于群体动态监测而言,主要监测群体近交程度、遗传多样性、群体结构以及种群特性生产性状等变化情况等。近交系数最初由Wright S. (1921年)提出,在假定群体中祖先没有亲缘关系的前提下,通过通径原理分析计算得到的。利用系谱信息估测亲缘关系是通过基因组IBD概率的统计期望值,而利用基因组信息可以估测个体间实际的亲缘关系。在系谱信息缺少的情况下,可以采用FROH估计其群体近交系数。如果ROH>5 Mb时,其基于系谱估测的平均值与FROH值相关系数为0.87,而当ROH<5 Mb时,其基于系谱估测平均值与FROH值相关性较小[16,24],在实际应用中,可以结合系谱信息,采用较大的ROH估测群体基因组近交系数。近交群体会产生近交衰退现象,近交衰退是由于基因组纯合片段增多引起的现象,在生产实践中,由于近交衰退导致群体整体生产性能会逐渐下降,对于畜禽保种和育种管理者而言,研究近交衰退以及由此引起群体生产性能下降是一个比较重要的课题。采用ROH信息已经成功定位人类许多罕见隐性疾病的致病基因[41],这对于研究群体种公畜遗传缺陷的致病机理具有很高的借鉴作用,也为规范种畜禽市场提供检测依据。另外,充分利用ROH信息挖掘畜禽群体适应性、繁殖力、耐粗饲等性状的特有基因更有利于畜禽保种场保护与利用工作的有序开展。在生物大数据时代下,畜禽遗传资源保护与利用工作也需要不断调整研究思路和策略来迎合和充分利用高通量测序技术进步带来的福祉。

4 结语与展望

本文全面总结了畜禽基因组中ROH发展历史、鉴定方法以及在群体结构、基因组功能分析和种畜禽品质检测等方面的应用。综上所述,ROH在畜禽基因组中是普遍存在的,通过分析基因组中分布的ROH,人们可以了解群体近交程度、群体多样性以及种公畜(禽)遗传缺陷等。但是,目前研究的物种主要集中在奶牛和猪中,在肉牛和其他家畜以及家禽中研究的较少,今后需要加大对马、驴、绵羊、山羊和家禽等畜禽基因组中ROH的研究,从而更好地了解ROH在染色体上分布情况以及其作用机理。

目前,鉴定畜禽基因组中ROH没有统一的标准,在不同畜种的研究中采用不同算法和方法。迄今为止,已有的研究很少关注优化鉴定ROH的参数组合,如果使用最优参数组合会更好地理解基因组中纯合性形成的机制[81]。此外,畜禽基因组中鉴定ROH频率和分布受到许多因素的影响,ROH在染色体内和染色体之间分布频率差异大,因此在染色体上会出现ROH集中区域(也称ROH岛),也会出现ROH分布少的区域(也称ROH荒漠),但相关机理还有待于进一步研究。

2015年,动物基因组功能注解(Functional Annotation of Animal Genomes, FAANG)计划启动,充分说明农业动物领域相关研究的重要性[93]。随着畜禽基因组研究时代的到来,海量数据的获得便于更加系统地研究ROH特征序列、进一步剖析群体近交增量、群体演变历史、选择信号以及遗传疾病等机理,从而开启畜禽基因组研究运用于畜禽遗传资源保护与利用的新时代[94]。

The authors have declared that no competing interests exist.

作者已声明无竞争性利益关系。


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Gibson J, Morton NE, Collins A . Extended tracts of homozygosity in outbred human populations
Hum Mol Genet, 2006,15(5):789-795.
URLPMID:16436455 [本文引用: 3]
Abstract Long tracts of consecutive homozygous single nucleotide polymorphisms (SNPs) can arise in the genome through a number of mechanisms. These include inbreeding in which an individual inherits chromosomal segments that are identical by descent from each parent. However, recombination and other processes break up chromosomal segments over generations. The longest tracts are therefore to be expected in populations with an appreciable degree of inbreeding. We examined the length, number and distribution of long tracts of homozygosity in the apparently outbred HapMap populations. We observed 1393 tracts exceeding 1 Mb in length among the 209 unrelated HapMap individuals. The longest was an uninterrupted run of 3922 homozygous SNPs spanning 17.9 Mb in a Japanese individual. We find that homozygous tracts are significantly more common in regions with high linkage disequilibrium and low recombination, and the location of tracts is similar across all populations. The Yoruba sample has the fewest long tracts per individual, consistent with a larger number of generations (and hence amount of recombination) since the founding of that population. Our results suggest that multiple-megabase-scale ancestral haplotypes persist in outbred human populations in broad genomic regions which have lower than average recombination rates. We observed three outlying individuals who have exceptionally long and numerous homozygous tracts that are not associated with recombination suppressed areas of the genome. We consider that this reflects a high level of relatedness in their ancestry which is too recent to have been influenced by the local recombination intensity. Possible alternative mechanisms and the implications of long homozygous tracts in the genome are discussed.

McQuillan R, Leutenegger AL, Abdel-Rahman R, Franklin CS, Pericic M, Barac-Lauc L, Smolej-Narancic N, Janicijevic B, Polasek O, Tenesa A, Macleod AK, Farrington SM, Rudan P, Hayward C, Vitart V, Rudan I, Wild SH, Dunlop MG, Wright AF, Campbell H, Wilson JF . Runs of homozygosity in European populations
Am J Hum Genet, 2008,83(3):359-372.
URLPMID:18760389 [本文引用: 3]
Abstract Estimating individual genome-wide autozygosity is important both in the identification of recessive disease variants via homozygosity mapping and in the investigation of the effects of genome-wide homozygosity on traits of biomedical importance. Approaches have tended to involve either single-point estimates or rather complex multipoint methods of inferring individual autozygosity, all on the basis of limited marker data. Now, with the availability of high-density genome scans, a multipoint, observational method of estimating individual autozygosity is possible. Using data from a 300,000 SNP panel in 2618 individuals from two isolated and two more-cosmopolitan populations of European origin, we explore the potential of estimating individual autozygosity from data on runs of homozygosity (ROHs). Termed F(roh), this is defined as the proportion of the autosomal genome in runs of homozygosity above a specified length. Mean F(roh) distinguishes clearly between subpopulations classified in terms of grandparental endogamy and population size. With the use of good pedigree data for one of the populations (Orkney), F(roh) was found to correlate strongly with the inbreeding coefficient estimated from pedigrees (r = 0.86). Using pedigrees to identify individuals with no shared maternal and paternal ancestors in five, and probably at least ten, generations, we show that ROHs measuring up to 4 Mb are common in demonstrably outbred individuals. Given the stochastic variation in ROH number, length, and location and the fact that ROHs are important whether ancient or recent in origin, approaches such as this will provide a more useful description of genomic autozygosity than has hitherto been possible.

Johnson EC, Evans LM, Keller MC . Relationships between estimated autozygosity and complex traits in the UK Biobank
PLoS Genet, 2018,14(7):e1007556.
URL [本文引用: 1]

Ferencaković M, Hamzic E, Gredler B, Curik I, Sölkner J . Runs of homozygosity reveal genome-wide autozygosity in the Austrian Fleckvieh cattle
Agric Conspec Sci, 2011,76:286-293.
URL [本文引用: 3]
Runs of homozygosity (ROH) are recognized as potential inbreeding measure in studies on humans. Inbreeding coefficients derived from ROH (FROH) measure proportion of the genome arranged in long homozygous segments and highly correlate with those derived from pedigree (Fped). From that we assumed that ROH represent an alternative to pedigree inbreeding levels in studies on animals too, because pedigree can be incorrect, incomplete and can not fully explain what happened in meiosis. To confirm our premise we used pedigree and genotype data from 500 Austrian dual purpose Simmental bulls to determine correlation between FROH and Fped. ROH were obtainedusing Fortran 90 soft ware created by the authors. Proportions of genome in ROH were calculated for lengths of ROH of >1, >2, >4, >8 and >16 Mb. Pedigree data were analyzed and inbreeding coefficients for complete pedigree (FpedT) and five generations (Fped5) were calculated using ENDOG soft ware. We found low FpedT and Fped5 (means of 1.5% and 0.9%) while FROH for segments >1Mb suggested much higher values (9.0%) indicating old inbreeding that can not be traced using pedigree. The highest correlations were found between FROH calculated from ROH of length >4Mb and FpedT (0.68) that is consistent with studies on humans. We conclude that inbreeding coefficients derived from ROH are useful for measuring levels of inbreeding in cattle, because ROH are not subject to mistakes as pedigrees and calculations made from those.

Ferencaković M, Hamzić E, Gredler B, Solberg TR, Klemetsdal G, Curik I, Sölkner J . Estimates of autozygosity derived from runs of homozygosity: empirical evidence from selected cattle populations
J Anim Breed Genet, 2013,130(4):286-293.
URL [本文引用: 2]

Keller MC, Visscher PM, Goddard ME . Quantification of inbreeding due to distant ancestors and its detection using dense single nucleotide polymorphism data
Genetics, 2011,189(1):237-249.
URL [本文引用: 2]

Broman KW, Weber JL . Long homozygous chromosomal segments in reference families from the centre d'Etude du polymorphisme humain
Am J Hum Genet, 1999,65(6):1493-1500.
URL [本文引用: 2]

Bosse M, Megens HJ, Madsen O, Paudel Y, Frantz LA, Schook LB, Crooijmans RP, Groenen MA . Regions of homozygosity in the porcine genome: consequence of demography and the recombination landscape
PLoS Genet, 2012,8(11):e1003100.
URLPMID:23209444 [本文引用: 3]
Abstract Inbreeding has long been recognized as a primary cause of fitness reduction in both wild and domesticated populations. Consanguineous matings cause inheritance of haplotypes that are identical by descent (IBD) and result in homozygous stretches along the genome of the offspring. Size and position of regions of homozygosity (ROHs) are expected to correlate with genomic features such as GC content and recombination rate, but also direction of selection. Thus, ROHs should be non-randomly distributed across the genome. Therefore, demographic history may not fully predict the effects of inbreeding. The porcine genome has a relatively heterogeneous distribution of recombination rate, making Sus scrofa an excellent model to study the influence of both recombination landscape and demography on genomic variation. This study utilizes next-generation sequencing data for the analysis of genomic ROH patterns, using a comparative sliding window approach. We present an in-depth study of genomic variation based on three different parameters: nucleotide diversity outside ROHs, the number of ROHs in the genome, and the average ROH size. We identified an abundance of ROHs in all genomes of multiple pigs from commercial breeds and wild populations from Eurasia. Size and number of ROHs are in agreement with known demography of the populations, with population bottlenecks highly increasing ROH occurrence. Nucleotide diversity outside ROHs is high in populations derived from a large ancient population, regardless of current population size. In addition, we show an unequal genomic ROH distribution, with strong correlations of ROH size and abundance with recombination rate and GC content. Global gene content does not correlate with ROH frequency, but some ROH hotspots do contain positive selected genes in commercial lines and wild populations. This study highlights the importance of the influence of demography and recombination on homozygosity in the genome to understand the effects of inbreeding.

Herrero-Medrano JM, Megens HJ, Groenen MA, Ramis G, Bosse M, Pérez-Enciso M, Crooijmans RP . Conservation genomic analysis of domestic and wild pig populations from the Iberian Peninsula
BMC Genet, 2013,14:106.
URLPMID:3840735 [本文引用: 2]
Background Inbreeding is among the major concerns in management of local livestock populations. The effective population size of these populations tends to be small, which enhances the risk of fitness reduction and extinction. High-density SNP data make it possible to undertake novel approaches in conservation genetics of endangered breeds and wild populations. A total of 97 representative samples of domestic and wild pig populations from the Iberian Peninsula, subjected to different levels of threat with extinction, were genotyped with a 60 K SNP panel. Data analyses based on: (i) allele frequency differences; (ii) linkage disequilibrium and (iii) runs of homozygosity were integrated to study population relationships, inbreeding and demographic history. Results The domestic pigs analyzed belonged to local Spanish and Portuguese breeds: Iberian ??? including the variants Retinto Iberian, Negro Iberian and Manchado de Jabugo ???, Bisaro and Chato Murciano. The population structure and persistence of phase analysis suggested high genetic relations between Iberian variants, with recent crossbreeding of Manchado de Jabugo with other pig populations. Chato Murciano showed a high frequency of long runs of homozygosity indicating recent inbreeding and reflecting the recent bottleneck reported by historical records. The Chato Murciano and the Manchado de Jabugo breeds presented the lowest effective population sizes in accordance with their status of highly inbred breeds. The Iberian wild boar presented a high frequency of short runs of homozygosity indicating past small population size but no signs of recent inbreeding. The Iberian breed showed higher genetic similarities with Iberian wild boar than the other domestic breeds. Conclusions High-density SNP data provided a consistent overview of population structure, demographic history and inbreeding of minority breeds and wild pig populations from the Iberian Peninsula. Despite the very different background of the populations used, we found a good agreement between the different analyses. Our results are also in agreement with historical reports and provide insight in the events that shaped the current genetic variation of pig populations from the Iberian Peninsula. The results exposed will aid to design and implement strategies for the future management of endangered minority pig breeds and wild populations.

Purfield DC, Berry DP, McParland S, Bradley DG . Runs of homozygosity and population history in cattle
BMC Genet, 2012,13:70.
[本文引用: 4]

Kim ES, Cole JB, Huson H, Wiggans GR, Van Tassell CP, Crooker BA, Liu G, Da Y, Sonstegard TS . Effect of artificial selection on runs of homozygosity in u.s. Holstein cattle
PLoS One, 2013,8(11):e80813.
URLPMID:3858116 [本文引用: 2]
The intensive selection programs for milk made possible by mass artificial insemination increased the similarity among the genomes of North American (NA) Holsteins tremendously since the 1960s. This migration of elite alleles has caused certain regions of the genome to have runs of homozygosity (ROH) occasionally spanning millions of continuous base pairs at a specific locus. In this study, genome signatures of artificial selection in NA Holsteins born between 1953 and 2008 were identified by comparing changes in ROH between three distinct groups under different selective pressure for milk production. The ROH regions were also used to estimate the inbreeding coefficients. The comparisons of genomic autozygosity between groups selected or unselected since 1964 for milk production revealed significant differences with respect to overall ROH frequency and distribution. These results indicate selection has increased overall autozygosity across the genome, whereas the autozygosity in an unselected line has not changed significantly across most of the chromosomes. In addition, ROH distribution was more variable across the genomes of selected animals in comparison to a more even ROH distribution for unselected animals. Further analysis of genome-wide autozygosity changes and the association between traits and haplotypes identified more than 40 genomic regions under selection on several chromosomes (Chr) including Chr 2, 7, 16 and 20. Many of these selection signatures corresponded to quantitative trait loci for milk, fat, and protein yield previously found in contemporary Holsteins.

Zhang Q, Guldbrandtsen B, Bosse M, Lund MS, Sahana G . Runs of homozygosity and distribution of functional variants in the cattle genome
BMC Genomics, 2015,16:542.
URLPMID:4508970 [本文引用: 2]
Background Recent developments in sequencing technology have facilitated widespread investigations of genomic variants, including continuous stretches of homozygous genomic regions. For cattle, a large proportion of these runs of homozygosity (ROH) are likely the result of inbreeding due to the accumulation of elite alleles from long-term selective breeding programs. In the present study, ROH were characterized in four cattle breeds with whole genome sequence data and the distribution of predicted functional variants was detected in ROH regions and across different ROH length classes. Results On average, 19.5 % of the genome was located in ROH across four cattle breeds. There were an average of 715.5 ROH per genome with an average size of ~750 kbp, ranging from 10 (minimum size considered) to 49,290 kbp. There was a significant correlation between shared short ROH regions and regions putatively under selection (p???<???0.001). By investigating the relationship between ROH and the predicted deleterious and non-deleterious variants, we gained insight into the distribution of functional variation in inbred (ROH) regions. Predicted deleterious variants were more enriched in ROH regions than predicted non-deleterious variants, which is consistent with observations in the human genome. We also found that increased enrichment of deleterious variants was significantly higher in short (<100 kbp) and medium (0.1 to 3 Mbp) ROH regions compared with long (>3 Mbp) ROH regions (P???<???0.001), which is different than what has been observed in the human genome. Conclusions This study illustrates the distribution of ROH and functional variants within ROH in cattle populations. These patterns are different from those in the human genome but consistent with the natural history of cattle populations, which is confirmed by the significant correlation between shared short ROH regions and regions putatively under selection. These findings contribute to understanding the effects of inbreeding and probably selection in shaping the distribution of functional variants in the cattle genome.

Lencz T, Lambert C, DeRosse P, Burdick KE, Morgan TV, Kane JM, Kucherlapati R, Malhotra AK . Runs of homozygosity reveal highly penetrant recessive loci in schizophrenia
Proc Natl Acad Sci USA, 2007,104(50):19942-19947.
URL [本文引用: 1]

Megens HJ, Crooijmans RP, Bastiaansen JW, Kerstens HH, Coster A, Jalving R, Vereijken A, Silva P, Muir WM, Cheng HH, Hanotte O, Groenen MA . Comparison of linkage disequilibrium and haplotype diversity on macro- and microchromosomes in chicken
BMC Genet, 2009,10:86.
URLPMID:20021697 [本文引用: 1]
pAbstract/p pBackground/p pThe chicken (itGallus gallus/it), like most avian species, has a very distinct karyotype consisting of many micro- and a few macrochromosomes. While it is known that recombination frequencies are much higher for micro- as compared to macrochromosomes, there is limited information on differences in linkage disequilibrium (LD) and haplotype diversity between these two classes of chromosomes. In this study, LD and haplotype diversity were systematically characterized in 371 birds from eight chicken populations (commercial lines, fancy breeds, and red jungle fowl) across macro- and microchromosomes. To this end we sampled four regions of ~1 cM each on macrochromosomes (GGA1 and GGA2), and four 1.5 -2 cM regions on microchromosomes (GGA26 and GGA27) at a high density of 1 SNP every 2 kb (total of 889 SNPs)./p pResults/p pAt a similar physical distance, LD, haplotype homozygosity, haploblock structure, and haplotype sharing were all lower for the micro- as compared to the macrochromosomes. These differences were consistent across populations. Heterozygosity, genetic differentiation, and derived allele frequencies were also higher for the microchromosomes. Differences in LD, haplotype variation, and haplotype sharing between populations were largely in line with known demographic history of the commercial chicken. Despite very low levels of LD, as measured by rsup2 /supfor most populations, some haploblock structure was observed, particularly in the macrochromosomes, but the haploblock sizes were typically less than 10 kb./p pConclusion/p pDifferences in LD between micro- and macrochromosomes were almost completely explained by differences in recombination rate. Differences in haplotype diversity and haplotype sharing between micro- and macrochromosomes were explained by differences in recombination rate and genotype variation. Haploblock structure was consistent with demography of the chicken populations, and differences in recombination rates between micro- and macrochromosomes. The limited haploblock structure and LD suggests that future whole-genome marker assays will need 100+K SNPs to exploit haplotype information. Interpretation and transferability of genetic parameters will need to take into account the size of chromosomes in chicken, and, since most birds have microchromosomes, in other avian species as well./p

Kirin M, McQuillan R, Franklin CS, Campbell H, McKeigue PM, Wilson JF . Genomic runs of homozygosity record population history and consanguinity
PLoS One, 2010,5(11):e13996.
URLPMID:21085596 [本文引用: 2]
The human genome is characterised by many runs of homozygous genotypes, where identical haplotypes were inherited from each parent. The length of each run is determined partly by the number of generations since the common ancestor: offspring of cousin marriages have long runs of homozygosity (ROH), while the numerous shorter tracts relate to shared ancestry tens and hundreds of generations ago. Human populations have experienced a wide range of demographic histories and hold diverse cultural attitudes to consanguinity. In a global population dataset, genome-wide analysis of long and shorter ROH allows categorisation of the mainly indigenous populations sampled here into four major groups in which the majority of the population are inferred to have: (a) recent parental relatedness (south and west Asians); (b) shared parental ancestry arising hundreds to thousands of years ago through long term isolation and restricted effective population size (Ne), but little recent inbreeding (Oceanians); (c) both ancient and recent parental relatedness (Native Americans); and (d) only the background level of shared ancestry relating to continental Ne (predominantly urban Europeans and East Asians; lowest of all in sub-Saharan African agriculturalists), and the occasional cryptically inbred individual. Moreover, individuals can be positioned along axes representing this demographic historic space. Long runs of homozygosity are therefore a globally widespread and under-appreciated characteristic of our genomes, which record past consanguinity and population isolation and provide a distinctive record of the demographic history of an individual's ancestors. Individual ROH measures will also allow quantification of the disease risk arising from polygenic recessive effects.

Curik I, Ferencaković M, Sölkner J . Inbreeding and runs of homozygosity: a possible solution to an old problem
Livest Sci, 2014,166(1):26-34.
URL [本文引用: 3]
61The runs of homozygosity (ROH) concept is well suited for estimating inbreeding.61Length and distribution of ROH can help revealing a population07s demographic history.61ROH frequencies vary widely within and across chromosomes.61Bovine and porcine populations exhibit higher ROH inbreeding than human populations.

Nothnagel M, Lu TT, Kayser M, Krawczak M . Genomic and geographic distribution of SNP-defined runs of homozygosity in Europeans
Hum Mol Genet, 2010,19(15):2927-2935.
URLPMID:20462934 [本文引用: 1]
The availability of high-density panels of genetic polymorphisms has led to the discovery of extended regions of apparent autozygosity in the human genome. At the genotype level, these regions present as sizeable stretches, or 'runs', of homozygosity (ROH). Here, we investigated both the genomic and the geographic distribution of ROHs in a large European sample of individuals originating from 23 subpopulations. The genomic ROH distribution was found to be characterized by a pattern of highly significant non-uniformity that was virtually identical in all subpopulations studied. Some 77 chromosomal regions contained ROHs at considerable frequency, thereby forming 'ROH islands' that were not explicable by high linkage disequilibrium alone. At the geographic level, the number and cumulative length of ROHs followed a prominent South to North gradient in agreement with expectations from European population history. The individual ROH length, in contrast, showed only minor and unsystematic geographic variation. While our findings are thus consistent with a larger effective population size in Southern than in Northern Europe, combined with a higher historic population density and mobility, they also indicate that the patterns of meiotic recombination in humans must have been very similar throughout the continent. Extending previous reports of a strong correlation between geography and identity-by-state, our data show that the genomic identity-by-descent patterns of Europeans are also clinal. As a consequence, the planning, design and interpretation of ROH-based genetic studies must take sample origin into account in order for such studies to be sensible and valid.

Song NN, Zhong JC, Chai ZX, Wang Q, He SM, Wu JB, Jian SL, Ran Q, Meng X, Hu HC . The whole genome data analysis of Sanjiang cattle
Sci Agric Sin, 2017,50(01):183-194.
URL [本文引用: 1]
【目的】研究三江黄牛群体遗传多样性,从基因组层面讨论其群体遗传变异情况。【方法】提取50个体基因组总DNA,等浓度等体积混合,构建混合样本DNA池,利用CovarisS2进行随机打断基因组DNA,电泳回收长度500 bp的DNA片段,构建DNA文库。应用Illumina HiSeq 2000测序,最终得到测序数据。利用BWA软件将短序列比对到牛参考基因组(UMD 3.1),来检测三江黄牛基因组突变情况。SAMtools、Picard-tools、GATK、Reseqtools对重测序数据进行分析,Ensemb1、DAVID、dbSNP数据库对SNPs和indels进行注释。【结果】全基因组重测序分析共计得到77.8 Gb序列数据,测序深度为25.32×,覆盖率为99.31%。测序得到778 403 444个reads和77 840 344 400个碱基,比对到参考基因组(UMD 3.1)的reads为673 670 505,碱基为67 341 451 555,匹配率分别为86.55%和86.51%,成对比对上的reads数为635 242 898(81.61%),成对比对上的碱基数为63 512636 924(81.59%);共确定了20 477 130个SNPs位点和1 355 308个indels,其中2 147 988个SNPs(2.4%)和90 180个indels(6.7%)是新发现的。总SNPs中,鉴定出纯合SNPs989 686(4.83%),杂合SNPs19 487 444(95.17%),纯合/杂合SNP比为1:19.7。转换数为14 800 438个,颠换为6 680 058个,转换/颠换(TS/TV)为2.215。剪切位点突变SNP727个,开始密码子变非开始密码子SNP117个,提前终止密码子的SNP 530个,终止密码子变非终止密码子SNP88个。检测到非同义突变数为57 621,同义突变为83 797,非同义/同义比率为0.69。检测到非同义SNPs分布在9 017个基因上,其中发现567个基因与已报道的重要经济性状相符,肉质、抗病、产奶、生长性状、生殖等相关基因的数量分别为471、77、21、10、8个,其中包括功能相重叠的基因;indels数据中,缺失数量为693 180(51.15%),插入数量为662 148(48.85%),纯合indels数量为161 198(11.89%),杂合indels数量1 194 110(88.11%),大部分的变异都位于基因间隔区和内含子区;三江黄牛全基因组杂合度(H)、核苷酸多样性(Pi)及theta W分别为7.6×10~(-3)、0.0 039、0.0 040,说明其遗传多样性较为丰富。三江黄牛群体Tajima'D为-0.06 832,推测可能由于群体内存在不平衡选择所致。【结论】本研究为进一步分析与经济性状相关的遗传学机制和保护三江黄牛品种遗传多样性提供了基因组数据支持。
宋娜娜, 钟金城, 柴志欣, 汪琦, 何世明, 吴锦波, 蹇尚林, 冉强, 蒙欣, 胡红春 . 三江黄牛全基因组数据分析
中国农业科学, 2017,50(1):183-194.
URL [本文引用: 1]
【目的】研究三江黄牛群体遗传多样性,从基因组层面讨论其群体遗传变异情况。【方法】提取50个体基因组总DNA,等浓度等体积混合,构建混合样本DNA池,利用CovarisS2进行随机打断基因组DNA,电泳回收长度500 bp的DNA片段,构建DNA文库。应用Illumina HiSeq 2000测序,最终得到测序数据。利用BWA软件将短序列比对到牛参考基因组(UMD 3.1),来检测三江黄牛基因组突变情况。SAMtools、Picard-tools、GATK、Reseqtools对重测序数据进行分析,Ensemb1、DAVID、dbSNP数据库对SNPs和indels进行注释。【结果】全基因组重测序分析共计得到77.8 Gb序列数据,测序深度为25.32×,覆盖率为99.31%。测序得到778 403 444个reads和77 840 344 400个碱基,比对到参考基因组(UMD 3.1)的reads为673 670 505,碱基为67 341 451 555,匹配率分别为86.55%和86.51%,成对比对上的reads数为635 242 898(81.61%),成对比对上的碱基数为63 512636 924(81.59%);共确定了20 477 130个SNPs位点和1 355 308个indels,其中2 147 988个SNPs(2.4%)和90 180个indels(6.7%)是新发现的。总SNPs中,鉴定出纯合SNPs989 686(4.83%),杂合SNPs19 487 444(95.17%),纯合/杂合SNP比为1:19.7。转换数为14 800 438个,颠换为6 680 058个,转换/颠换(TS/TV)为2.215。剪切位点突变SNP727个,开始密码子变非开始密码子SNP117个,提前终止密码子的SNP 530个,终止密码子变非终止密码子SNP88个。检测到非同义突变数为57 621,同义突变为83 797,非同义/同义比率为0.69。检测到非同义SNPs分布在9 017个基因上,其中发现567个基因与已报道的重要经济性状相符,肉质、抗病、产奶、生长性状、生殖等相关基因的数量分别为471、77、21、10、8个,其中包括功能相重叠的基因;indels数据中,缺失数量为693 180(51.15%),插入数量为662 148(48.85%),纯合indels数量为161 198(11.89%),杂合indels数量1 194 110(88.11%),大部分的变异都位于基因间隔区和内含子区;三江黄牛全基因组杂合度(H)、核苷酸多样性(Pi)及theta W分别为7.6×10~(-3)、0.0 039、0.0 040,说明其遗传多样性较为丰富。三江黄牛群体Tajima'D为-0.06 832,推测可能由于群体内存在不平衡选择所致。【结论】本研究为进一步分析与经济性状相关的遗传学机制和保护三江黄牛品种遗传多样性提供了基因组数据支持。

Lan R, Zhu L, Shao QY, Hong QH . Whole-genome resequencing in Yunnan black goat
Grass-Feed Liv, 2016, ( 05):11-17.
URL [本文引用: 1]
采用Illumina Hiseq2000测序技术对由云南黑山羊具有代表性的个体构建的DNA池进行20X全基因组重测序,以期对云南黑山羊分子特征做出评价,并为云南黑山羊功能基因定位提供分子基础数据。结果表明:云南黑山羊可以检测到7 615 774个SNP、877 232个INDEL和40 005个SV。通过比对山羊参考基因组,并进行生物信息学分析,结果显示云南黑山羊位于外显子区域的SNP有35 902个,其中异义突变17 160个,同义突变18 920个;外显子区域的小INDEL有1 330个;位于内含子区域的SNP 1 695 420个,小INDEL 208 999,位于UTR3区域的SNP 16 106个,小INDEL 580个。研究结果基本阐明了云南黑山羊的分子特征,为后续功能基因的研究提供了强大的数据支撑,并为功能基因的定位提供新的思路和线索。
兰蓉, 朱兰, 邵庆勇, 洪琼花 . 云南黑山羊全基因组重测序
草食家畜, 2016, ( 5):11-17.
URL [本文引用: 1]
采用Illumina Hiseq2000测序技术对由云南黑山羊具有代表性的个体构建的DNA池进行20X全基因组重测序,以期对云南黑山羊分子特征做出评价,并为云南黑山羊功能基因定位提供分子基础数据。结果表明:云南黑山羊可以检测到7 615 774个SNP、877 232个INDEL和40 005个SV。通过比对山羊参考基因组,并进行生物信息学分析,结果显示云南黑山羊位于外显子区域的SNP有35 902个,其中异义突变17 160个,同义突变18 920个;外显子区域的小INDEL有1 330个;位于内含子区域的SNP 1 695 420个,小INDEL 208 999,位于UTR3区域的SNP 16 106个,小INDEL 580个。研究结果基本阐明了云南黑山羊的分子特征,为后续功能基因的研究提供了强大的数据支撑,并为功能基因的定位提供新的思路和线索。

Mei CG, Wang HC, Zan LS, Cheng G, Li AP, Zhao CP, Wang HB . Research progress on animal genome research based on high-throughput sequencing technology
J Northwest Sci-Tech Univ Agric Fore(Nat Sci Ed), 2016,44(3):43-51.
URL [本文引用: 3]
动物基因组学研究是进行动物遗传资源保护和利用以及分子育种的一项重要基础工作,高通量测序技术的出现为动物基因组学研究带来了革命性飞跃。文章对基于高通量测序技术的动物基因组从头测序、重测序、简化基因组测序等基因组学研究进行了综述,总结了相关的生物信息分析内容,并对不同分析工具及方法进行了比较分析。最后,讨论了当前高通量测序技术存在的问题,对该技术未来发展方向进行了展望。
梅楚刚, 王洪程, 昝林森, 成功, 李安宁, 赵春平, 王洪宝 . 基于高通量测序的动物基因组研究进展
西北农林科技大学学报(自然科学版), 2016,44(3):43-51.
URL [本文引用: 3]
动物基因组学研究是进行动物遗传资源保护和利用以及分子育种的一项重要基础工作,高通量测序技术的出现为动物基因组学研究带来了革命性飞跃。文章对基于高通量测序技术的动物基因组从头测序、重测序、简化基因组测序等基因组学研究进行了综述,总结了相关的生物信息分析内容,并对不同分析工具及方法进行了比较分析。最后,讨论了当前高通量测序技术存在的问题,对该技术未来发展方向进行了展望。

Marras G, Gaspa G, Sorbolini S, Dimauro C, Ajmone- Marsan P, Valentini A, Williams JL, Macciotta NP . Analysis of runs of homozygosity and their relationship with inbreeding in five cattle breeds farmed in Italy
Anim Genet, 2015,46(2):110-121.
URLPMID:25530322 [本文引用: 2]
Summary Increased inbreeding is an inevitable consequence of selection in livestock populations. The analysis of high-density single nucleotide polymorphisms (SNPs) facilitates the identification of long and uninterrupted runs of homozygosity (ROH) that can be used to identify chromosomal regions that are identical by descent. In this work, the distribution of ROH of different lengths in five Italian cattle breeds is described. A total of 4095 bulls from five cattle breeds (2093 Italian Holstein, 749 Italian Brown, 364 Piedmontese, 410 Marchigiana and 479 Italian Simmental) were genotyped at 54K SNP loci. ROH were identified and used to estimate molecular inbreeding coefficients ( F ROH), which were compared with inbreeding coefficients estimated from pedigree information ( F PED) and using the genomic relationship matrix ( F GRM). The average number of ROH per animal ranged from 5402±027.2 in Piedmontese to 94.602±0211.6 in Italian Brown. The highest number of short ROH (related to ancient consanguinity) was found in Piedmontese, followed by Simmental. The Italian Brown and Holstein had a higher proportion of longer ROH distributed across the whole genome, revealing recent inbreeding. The F PED were moderately correlated with F ROH02>02102Mb (0.662, 0.700 and 0.669 in Italian Brown, Italian Holstein and Italian Simmental respectively) but poorly correlated with F GRM (0.134, 0.128 and 0.448 for Italian Brown, Italian Holstein and Italian Simmental respectively). The inclusion of ROH02>02802Mb in the inbreeding calculation improved the correlation of F ROH with F PED and F GRM. ROH are a direct measure of autozygosity at the DNA level and can overcome approximations and errors resulting from incomplete pedigree data. In populations with high linkage disequilibrium (LD) and recent inbreeding (e.g. Italian Holstein and Italian Brown), a medium-density marker panel, such as the one used here, may provide a good estimate of inbreeding. However, in populations with low LD and ancient inbreeding, marker density would have to be increased to identify short ROH that are identical by descent more precisely.

Williams JL, Hall SJ, Del Corvo M, Ballingall KT, Colli L, Ajmone Marsan P, Biscarini F . Inbreeding and purging at the genomic Level: the Chillingham cattle reveal extensive, non-random SNP heterozygosity
Anim Genet, 2016,47(1):19-27.
URLPMID:26559490
Summary Local breeds of livestock are of conservation significance as components of global biodiversity and as reservoirs of genetic variation relevant to the future sustainability of agriculture. One such rare historic breed, the Chillingham cattle of northern England, has a 350-year history of isolation and inbreeding yet shows no diminution of viability or fertility. The Chillingham cattle have not been subjected to selective breeding. It has been suggested previously that the herd has minimal genetic variation. In this study, high-density SNP genotyping with the 777K SNP chip showed that 9.1% of loci on the chip are polymorphic in the herd, compared with 62–90% seen in commercial cattle breeds. Instead of being homogeneously distributed along the genome, these loci are clustered at specific chromosomal locations. A high proportion of the Chillingham individuals examined were heterozygous at many of these polymorphic loci, suggesting that some loci are under balancing selection. Some of these frequently heterozygous loci have been implicated as sites of recessive lethal mutations in cattle. Linkage disequilibrium equal or close to 100% was found to span up to 135002kb, and LD was above r 202=020.25 up to more than 500002kb. This strong LD is consistent with the lack of polymorphic loci in the herd. The heterozygous regions in the Chillingham cattle may be the locations of genes relevant to fitness or survival, which may help elucidate the biology of local adaptation in traditional breeds and facilitate selection for such traits in commercial cattle.

Signer-Hasler H, Burren A, Neuditschko M, Frischknecht M, Garrick D, Stricker C, Gredler B, Bapst B, Flury C . Population structure and genomic inbreeding in nine Swiss dairy cattle populations
Genet Sel Evol, 2017,49(1):83.
URL

Mastrangelo S, Sardina MT, Tolone M, Di Gerlando R, Sutera AM, Fontanesi L, Portolano B . Genome-wide identification of runs of homozygosity islands and associated genes in local dairy cattle breeds
Animal, 2018, 1-9.
URL [本文引用: 4]

Zhang Y, Young JM, Wang C, Sun X, Wolc A, Dekkers JCM. Inbreeding by pedigree and genomic markers in selection lines of pigs
In:Proceedings of the 10th World Congress of Genetics Applied to Livestock Production. Vancouver, BC, Canada, 2014.
[本文引用: 3]

Saura M, Fernández A, Varona L, Fernández AI, de Cara Má, Barragán C, Villanueva B . Detecting inbreeding depression for reproductive traits in Iberian pigs using genome-wide data
Genet Sel Evol, 2015,47:1.
URLPMID:25595431 [本文引用: 2]
Background The current availability of genotypes for very large numbers of single nucleotide polymorphisms (SNPs) is leading to more accurate estimates of inbreeding coefficients and more detailed approaches for detecting inbreeding depression. In the present study, genome-wide information was used to detect inbreeding depression for two reproductive traits (total number of piglets born and number of piglets born alive) in an ancient strain of Iberian pigs (the Guadyerbas strain) that is currently under serious danger of extinction. Methods A total of 109 sows with phenotypic records were genotyped with the PorcineSNP60 BeadChip v1. Inbreeding depression was estimated using a bivariate animal model in which the inbreeding coefficient was included as a covariate. We used two different measures of genomic inbreeding to perform the analyses: inbreeding estimated on a SNP-by-SNP basis and inbreeding estimated from runs of homozygosity. We also performed the analyses using pedigree-based inbreeding. Results Significant inbreeding depression was detected for both traits using all three measures of inbreeding. Genome-wide information allowed us to identify one region on chromosome 13 associated with inbreeding depression. This region spans from 27 to 54 Mb and overlaps with a previously detected quantitative trait locus and includes the inter-alpha-trypsin inhibitor gene cluster that is involved with embryo implantation. Conclusions Our results highlight the value of high-density SNP genotyping for providing new insights on where genes causing inbreeding depression are located in the genome. Genomic measures of inbreeding obtained on a SNP-by-SNP basis or those based on the presence/absence of runs of homozygosity represent a suitable alternative to pedigree-based measures to detect inbreeding depression, and a useful tool for mapping studies. To our knowledge, this is the first study in domesticated animals using the SNP-by-SNP inbreeding coefficient to map specific regions within chromosomes associated with inbreeding depression.

Traspov A, Deng W, Kostyunina O, Ji J, Shatokhin K, Lugovoy S, Zinovieva N, Yang B, Huang L . Population structure and genome characterization of local pig breeds in Russia, Belorussia, Kazakhstan and Ukraine
Genet Sel Evol, 2016,48:16.
URLPMID:4980786
It is generally accepted that domestication of pigs took place in multiple locations across Eurasia; the breeds that originated in Europe and Asia have been well studied. However, the genetic structure of pig breeds from Russia, Belorussia, Kazakhstan and Ukraine, which represent large geographical areas and diverse climatic zones in Eurasia, remains largely unknown. This study provides the first genomic survey of 170 pigs representing 13 breeds from Russia, Belorussia, Kazakhstan and Ukraine; 288 pigs from six Chinese and seven European breeds were also included for comparison. Our findings show that the 13 novel breeds tested derived mainly from European pigs through the complex admixture of Large White, Landrace, Duroc, Hampshire and other breeds, and that they display no geographic structure based on genetic distance. We also found a considerable Asian contribution to the miniature Siberian pigs (Minisib breed) from Russia. Apart from the Minisib, Urzhum, Ukrainian Spotted Steppe and Ukrainian White Steppe breeds, which may have undergone intensive inbreeding, the breeds included in this study showed relatively high genetic diversity and low levels of homozygosity compared to the Chinese indigenous pig breeds. This study provides the first genomic overview of the population structure and genetic diversity of 13 representative pig breeds from Russia, Belorussia, Kazakhstan and Ukraine; this information will be useful for the preservation and management of these breeds. The online version of this article (doi:10.1186/s12711-016-0196-y) contains supplementary material, which is available to authorized users.

Yang B, Cui L, Perez-Enciso M, Traspov A, Crooijmans RPMA, Zinovieva N, Schook LB, Archibald A, Gatphayak K, Knorr C, Triantafyllidis A, Alexandri P, Semiadi G, Hanotte O, Dias D, Dovc P, Uimari P, Iacolina L, Scandura M, Groenen MAM, Huang L, Megens HJ . Genome-wide SNP data unveils the globalization of domesticated pigs
Genet Sel Evol, 2017,49(1):71.
URLPMID:5609043
Abstract Background Pigs were domesticated independently in Eastern and Western Eurasia early during the agricultural revolution, and have since been transported and traded across the globe. Here, we present a worldwide survey on 60K genome-wide single nucleotide polymorphism (SNP) data for 2093 pigs, including 1839 domestic pigs representing 122 local and commercial breeds, 215 wild boars, and 39 out-group suids, from Asia, Europe, America, Oceania and Africa. The aim of this study was to infer global patterns in pig domestication and diversity related to demography, migration, and selection. Results A deep phylogeographic division reflects the dichotomy between early domestication centers. In the core Eastern and Western domestication regions, Chinese pigs show differentiation between breeds due to geographic isolation, whereas this is less pronounced in European pigs. The inferred European origin of pigs in the Americas, Africa, and Australia reflects European expansion during the sixteenth to nineteenth centuries. Human-mediated introgression, which is due, in particular, to importing Chinese pigs into the UK during the eighteenth and nineteenth centuries, played an important role in the formation of modern pig breeds. Inbreeding levels vary markedly between populations, from almost no runs of homozygosity (ROH) in a number of Asian wild boar populations, to up to 20% of the genome covered by ROH in a number of Southern European breeds. Commercial populations show moderate ROH statistics. For domesticated pigs and wild boars in Asia and Europe, we identified highly differentiated loci that include candidate genes related to muscle and body development, central nervous system, reproduction, and energy balance, which are putatively under artificial selection. Conclusions Key events related to domestication, dispersal, and mixing of pigs from different regions are reflected in the 60K SNP data, including the globalization that has recently become full circle since Chinese pig breeders in the past decades started selecting Western breeds to improve local Chinese pigs. Furthermore, signatures of ongoing and past selection, acting at different times and on different genetic backgrounds, enhance our insight in the mechanism of domestication and selection. The global diversity statistics presented here highlight concerns for maintaining agrodiversity, but also provide a necessary framework for directing genetic conservation.

Lago LV, Nery da Silva A, Zanella EL, Groke Marques M, Peixoto JO, da Silva MVGB, Ledur MC, Zanella R . Identification of genetic regions associated with scrotal hernias in a commercial swine herd
Vet Sci, 2018,5(1). doi: 10.3390/vetsci5010015.
URLPMID:29382056 [本文引用: 1]
Abstract In this paper, we have used two approaches to detect genetic associations with scrotal hernias in commercial pigs. Firstly, we have investigated the effects of runs of homozygosity (ROH) with the appearance of scrotal hernias, followed by a Genome Wide Association Study (GWAS). The phenotype classification was based on visual appearance of scrotal hernias. Each affected animal was matched to a healthy control from the same pen. In the total, 68 animals were genotyped using the Porcine SNP60 Beadchip, out of those, 41 animals had the presence of hernias and 27 were healthy animals. Fifteen animals were removed from the analysis due to differences in genetic background, leaving 18 healthy animals and 35 piglets with scrotal hernia. Further, the detection of extended haplotypes shared ROH were conducted for health (control) and affected (case) animals and a permutation test was used to test whether the ROH segments were more frequent in case/case pairs than non-case/case pairs. Using the ROH, we have identified an association ( p = 0.019) on chromosome 2(SSC2) being segregated on animals with the presence of scrotal hernias. Using a GWAS, a region composed by 3 SNPs on the sexual chromosome X (SSCX) were associated with scrotal hernias ( p < 1.6 10 -5 ), this region harbors the Androgen Receptor Gene ( AR ).

Khanshour AM . Genetic diversity and population structure of the Arabian horse populations from Syria and other countries[D]. Texas A&M University, College Station, 2013a.
[本文引用: 1]

Metzger J, Karwath M, Tonda R, Beltran S, águeda L, Gut M, Gut IG, Distl O . Runs of homozygosity reveal signatures of positive selection for reproduction traits in breed and non-breed horses
BMC Genomics, 2015,16:764.
URLPMID:4600213 [本文引用: 4]
Modern horses represent heterogeneous populations specifically selected for appearance and performance. Genomic regions under high selective pressure show characteristic runs of homozygosity (ROH) which represent a low genetic diversity. This study aims at detecting the number and functional distribution of ROHs in different horse populations using next generation sequencing data. Next generation sequencing was performed for two Sorraia, one D眉lmen Horse, one Arabian, one Saxon-Thuringian Heavy Warmblood, one Thoroughbred and four Hanoverian. After quality control reads were mapped to the reference genome EquCab2.70. ROH detection was performed using PLINK, version 1.07 for a trimmed dataset with 11,325,777 SNPs and a mean read depth of 12. Stretches with homozygous genotypes of >40 kb as well as >400 kb were defined as ROHs. SNPs within consensus ROHs were tested for neutrality. Functional classification was done for genes annotated within ROHs using PANTHER gene list analysis and functional variants were tested for their distribution among breed or non-breed groups. ROH detection was performed using whole genome sequences of ten horses of six populations representing various breed types and non-breed horses. In total, an average number of 3492 ROHs were detected in windows of a minimum of 50 consecutive homozygous SNPs and an average number of 292 ROHs in windows of 500 consecutive homozygous SNPs. Functional analyses of private ROHs in each horse revealed a high frequency of genes affecting cellular, metabolic, developmental, immune system and reproduction processes. In non-breed horses, 198 ROHs in 50-SNP windows and seven ROHs in 500-SNP windows showed an enrichment of genes involved in reproduction, embryonic development, energy metabolism, muscle and cardiac development whereas all seven breed horses revealed only three common ROHs in 50-SNP windows harboring the fertility-related gene YES1. In the Hanoverian, a total of 18 private ROHs could be shown to be located in the region of genes potentially involved in neurologic control, signaling, glycogen balance and reproduction. Comparative analysis of homozygous stretches common in all ten horses displayed three ROHs which were all located in the region of KITLG, the ligand of KIT known to be involved in melanogenesis, haematopoiesis and gametogenesis. The results of this study give a comprehensive insight into the frequency and number of ROHs in various horses and their potential influence on population diversity and selection pressures. Comparisons of breed and non-breed horses suggest a significant artificial as well as natural selection pressure on reproduction performance in all types of horse populations. The online version of this article (doi:10.1186/s12864-015-1977-3) contains supplementary material, which is available to authorized users.

Druml T, Neuditschko M, Grilz-Seger G, Horna M, Ricard A, Mesaric M, Cotman M, Pausch H, Brem G . Population Networks Associated with Runs of Homozygosity Reveal New Insights into the Breeding History of the Haflinger Horse
J Hered, 2018,109(4):384-392.
URLPMID:29294044 [本文引用: 1]
In this study we analysed the genetic variability of the Austrian Haflinger horse population by use of pedigree analysis. For the analysis of inbreeding and genetic variability we defined three different reference populations which included active breeding animals animals between 1978 and 1985 (reference population 3, R3) comprised 6,34%, the effective number of founders was 43 and the... [Show full abstract]

Metzger J, Rau J, Naccache F, Bas Conn L, Lindgren G, Distl O . Genome data uncover four synergistic key regulators for extremely small body size in horses
BMC Genomics, 2018,19(1):492.
URL [本文引用: 1]
Miniature size in horses represents an extreme reduction of withers height that originated after domestication. In some breeds, it is a highly desired trait representing a breed- or subtype-specific feature. The genomic changes that emerged due to strong-targeted selection towards this distinct type remain unclear. Comparisons of whole-genome sequencing data from two Miniature Shetland ponies and one standard-sized Shetland pony, performed to elucidate genetic determinants for miniature size, revealed four synergistic variants, limiting withers height to 34.25 in. (87 cm). Runs of homozygosity regions were detected spanning these four variants in both the Miniature Shetland ponies and the standard-sized Shetland pony. They were shown to be characteristic of the Shetland pony breed, resulting in a miniature type under specific genotypic combinations. These four genetic variants explained 72% of the size variation among Shetland ponies and related breeds. The length of the homozygous regions indicate that they arose over 1000 years ago. In addition, a copy number variant was identified inDIAPH3harboring a loss exclusively in ponies and donkeys and thus representing a potential height-associated variant. This study reveals main drivers for miniature size in horses identified in whole genome data and thus provides relevant candidate genes for extremely short stature in mammals. The online version of this article (10.1186/s12864-018-4877-5) contains supplementary material, which is available to authorized users.

Beynon SE, Slavov GT, Farré M, Sunduimijid B, Waddams K, Davies B, Haresign W, Kijas J, MacLeod IM, Newbold CJ, Davies L, Larkin DM . Population structure and history of the Welsh sheep breeds determined by whole genome genotyping
BMC Genet, 2015,16:65.
URLPMID:26091804 [本文引用: 1]
Background One of the most economically important areas within the Welsh agricultural sector is sheep farming, contributing around ??230 million to the UK economy annually. Phenotypic selection over several centuries has generated a number of native sheep breeds, which are presumably adapted to the diverse and challenging landscape of Wales. Little is known about the history, genetic diversity and relationships of these breeds with other European breeds. We genotyped 353 individuals from 18 native Welsh sheep breeds using the Illumina OvineSNP50 array and characterised the genetic structure of these breeds. Our genotyping data were then combined with, and compared to, those from a set of 74 worldwide breeds, previously collected during the International Sheep Genome Consortium HapMap project. Results Model based clustering of the Welsh and European breeds indicated shared ancestry. This finding was supported by multidimensional scaling analysis (MDS), which revealed separation of the European, African and Asian breeds. As expected, the commercial Texel and Merino breeds appeared to have extensive co-ancestry with most European breeds. Consistently high levels of haplotype sharing were observed between native Welsh and other European breeds. The Welsh breeds did not, however, form a genetically homogeneous group, with pairwise FST between breeds averaging 0.107 and ranging between 0.020 and 0.201. Four subpopulations were identified within the 18 native breeds, with high homogeneity observed amongst the majority of mountain breeds. Recent effective population sizes estimated from linkage disequilibrium ranged from 88 to 825. Conclusions Welsh breeds are highly diverse with low to moderate effective population sizes and form at least four distinct genetic groups. Our data suggest common ancestry between the native Welsh and European breeds. These findings provide the basis for future genome-wide association studies and a first step towards developing genomics assisted breeding strategies in the UK.

Muchadeyi FC, Malesa MT, Soma P, Dzomba EF. Runs of homozygosity in Swakara pelt producing sheep: implications on sub-vital performance
In:Proceedings for Association for the Advancement of Animal Breeding and Genetics, 2015,21:310-313.
[本文引用: 2]

Purfield DC, McParland S, Wall E, Berry DP . The distribution of runs of homozygosity and selection signatures in six commercial meat sheep breeds
PLoS One, 2017,12(5):e0176780.
URLPMID:28463982 [本文引用: 1]
Domestication and the subsequent selection of animals for either economic or morphological features can leave a variety of imprints on the genome of a population. Genomic regions subjected to high selective pressures often show reduced genetic diversity and frequent runs of homozygosity (ROH). Therefore, the objective of the present study was to use 42,182 autosomal SNPs to identify genomic regions in 3,191 sheep from six commercial breeds subjected to selection pressure and to quantify the genetic diversity within each breed using ROH. In addition, the historical effective population size of each breed was also estimated and, in conjunction with ROH, was used to elucidate the demographic history of the six breeds. ROH were common in the autosomes of animals in the present study, but the observed breed differences in patterns of ROH length and burden suggested differences in breed effective population size and recent management. ROH provided a sufficient predictor of the pedigree inbreeding coefficient, with an estimated correlation between both measures of 0.62. Genomic regions under putative selection were identified using two complementary algorithms; the fixation index and hapFLK. The identified regions under putative selection included candidate genes associated with skin pigmentation, body size and muscle formation; such characteristics are often sought after in modern-day breeding programs. These regions of selection frequently overlapped with high ROH regions both within and across breeds. Multiple yet uncharacterised genes also resided within putative regions of selection. This further substantiates the need for a more comprehensive annotation of the sheep genome as these uncharacterised genes may contribute to traits of interest in the animal sciences. Despite this, the regions identified as under putative selection in the current study provide an insight into the mechanisms leading to breed differentiation and genetic variation in meat production.

Mastrangelo S, Tolone M, Sardina MT, Sottile G, Sutera AM, Di Gerlando R, Portolano B . Genome-wide scan for runs of homozygosity identifies potential candidate genes associated with local adaptation in Valle del Belice sheep
Genet Sel Evol, 2017,49(1):84.
URLPMID:5684758 [本文引用: 1]
Because very large numbers of single nucleotide polymorphisms (SNPs) are now available throughout the genome, they are particularly suitable for the detection of genomic regions where a reduction in heterozygosity has occurred and they offer new opportunities to improve the accuracy of inbreeding (\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$F$$\end{document}F) estimates. Runs of homozygosity (ROH) are contiguous lengths of homozygous segments of the genome where the two haplotypes inherited from the parents are identical. Here, we investigated the occurrence and distribution of ROH using a medium-dense SNP panel to characterize autozygosity in 516 Valle del Belice sheep and to identify the genomic regions with high ROH frequencies. We identified 11,629 ROH and all individuals displayed at least one ROH longer than 1 Mb. The mean value of\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$F$$\end{document}Festimated from ROH longer than1 Mb was 0.084 0.061. ROH that were shorter than 10 Mb predominated. The highest and lowest coverages ofOvis arieschromosomes (OAR) by ROH were on OAR24 and OAR1, respectively. The number of ROH per chromosome length displayed a specific pattern, with higher values for the first three chromosomes. Both number of ROH and length of the genome covered by ROH varied considerably between animals. Two hundred and thirty-nine SNPs were considered as candidate markers that may be under directional selection and we identified 107 potential candidate genes. Six genomic regions located on six chromosomes, corresponding to ROH islands, are presented as hotspots of autozygosity, which frequently coincided with regions of medium recombination rate. According to the KEGG database, most of these genes were involved in multiple signaling and signal transduction pathways in a wide variety of cellular and biochemical processes. A genome scan revealed the presence of ROH islands in genomic regions that harbor candidate genes for selection in response to environmental stress and which underlie local adaptation. These results suggest that natural selection has, at least partially, a role in shaping the genome of Valle del Belice sheep and that ROH in the ovine genome may help to detect genomic regions involved in the determinism of traits under selection. The online version of this article (10.1186/s12711-017-0360-z) contains supplementary material, which is available to authorized users.

Guangul SA . Design of community based breeding programs for two indigenous goat breeds of Ethiopia
[D]. University of Natural Resources and Life Sciences, 2014.
[本文引用: 3]

Onzima RB, Upadhyay MR, Doekes HP, Brito LF, Bosse M, Kanis E, Groenen MAM, Crooijmans RPMA . Genome-Wide characterization of selection signatures and runs of homozygosity in ugandan goat breeds
Front Genet, 2018,9:318.
URL [本文引用: 1]

Fleming DS, Koltes JE, Markey AD, Schmidt CJ, Ashwell CM, Rothschild MF, Persia ME, Reecy JM, Lamont SJ . Genomic analysis of Ugandan and Rwandan chicken ecotypes using a 600 k genotyping array
BMC Genomics, 2016,17:407.
URLPMID:27230772 [本文引用: 2]
Indigenous populations of animals have developed unique adaptations to their local environments, which may include factors such as response to thermal stress, drought, pathogens and suboptimal nutrition. The survival and subsequent evolution within these local environments can be the result of both natural and artificial selection driving the acquisition of favorable traits, which over time leave genomic signatures in a population. This study’s goals are to characterize genomic diversity and identify selection signatures in chickens from equatorial Africa to identify genomic regions that may confer adaptive advantages of these ecotypes to their environments. Indigenous chickens from Uganda (n=6572) and Rwanda (n=65100), plus Kuroilers (n=6524, an Indian breed imported to Africa), were genotyped using the Axiom03 60002k Chicken Genotyping Array. Indigenous ecotypes were defined based upon location of sampling within Africa. The results revealed the presence of admixture among the Ugandan, Rwandan, and Kuroiler populations. Genes within runs of homozygosity consensus regions are linked to gene ontology (GO) terms related to lipid metabolism, immune functions and stress-mediated responses (FDR65<650.15). The genes within regions of signatures of selection are enriched for GO terms related to health and oxidative stress processes. Key genes in these regions had anti-oxidant, apoptosis, and inflammation functions. The study suggests that these populations have alleles under selective pressure from their environment, which may aid in adaptation to harsh environments. The correspondence in gene ontology terms connected to stress-mediated processes across the populations could be related to the similarity of environments or an artifact of the detected admixture. The online version of this article (doi:10.1186/s12864-016-2711-5) contains supplementary material, which is available to authorized users.

Fleming DS, Weigend S, Simianer H, Weigend A, Rothschild M, Schmidt C, Ashwell C, Persia M, Reecy J, Lamont SJ . Genomic comparison of indigenous african and northern european chickens reveals putative mechanisms of stress tolerance related to environmental selection pressure
G3 (Bethesda), 2017,7(5):1525-1537.
URLPMID:5427493 [本文引用: 3]
Global climate change is increasing the magnitude of environmental stressors, such as temperature, pathogens, and drought, that limit the survivability and sustainability of livestock production. Poultry production and its expansion is dependent upon robust animals that are able to cope with stressors in multiple environments. Understanding the genetic strategies that indigenous, noncommercial breeds have evolved to survive in their environment could help to elucidate molecular mechanisms underlying biological traits of environmental adaptation. We examined poultry from diverse breeds and climates of Africa and Northern Europe for selection signatures that have allowed them to adapt to their indigenous environments. Selection signatures were studied using a combination of population genomic methods that employedFST, integrated haplotype score (iHS), and runs of homozygosity (ROH) procedures. All the analyses indicated differences in environment as a driver of selective pressure in both groups of populations. The analyses revealed unique differences in the genomic regions under selection pressure from the environment for each population. The African chickens showed stronger selection toward stress signaling and angiogenesis, while the Northern European chickens showed more selection pressure toward processes related to energy homeostasis. The results suggest that chromosomes 2 and 27 are the most diverged between populations and the most selected upon within the African (chromosome 27) and Northern European (chromosome 2) birds. Examination of the divergent populations has provided new insight into genes under possible selection related to tolerance of a population indigenous environment that may be baselines for examining the genomic contribution to tolerance adaptions.

Zhang M, Han W, Tang H, Li G, Zhang M, Xu R, Liu Y, Yang T, Li W, Zou J, Wu K . Genomic diversity dynamics in conserved chicken populations are revealed by genome-wide SNPs
BMC Genomics, 2018,19(1):598.
URL [本文引用: 2]
Maintaining maximum genetic diversity and preserving breed viability in conserved populations necessitates the rigorous evaluation of conservation schemes. Three chicken breeds (Baier Yellow Chicken (BEC), Beijing You Chicken (BYC) and Langshan Chicken (LSC)) are currently in conservation programs in China. Changes in genetic diversity were measured by heterozygosity, genomic inbreeding coefficients, and autozygosity, using estimates derived from runs of homozygosity (ROH) that were identified using SNPs. Ninety DNA samples were collected from three generations for each breed. In the most recent generation, the highest genetic diversity was observed in LSC, followed by BEC and BYC. Inbreeding coefficients based on ROH for the three breeds declined slightly between the first and middle generations, and then rapidly increased. No inbreeding coefficients exceeded 0.1. Population structure assessments using neighbor-joining tree analysis, principal components analysis, and STRUCTURE analysis indicated that no genetic differentiation existed within breeds. LD decay and ROH at different cut-off lengths were used to identify traces left by recent or ancient inbreeding. Few long ROH were identified, indicating that inbreeding has been largely avoided with the current conservation strategy. The observed losses in genetic diversity and occurrences of inbreeding might be consequences of sub-optimal effective population sizes. The conserved Chinese chicken populations have high genomic diversity under the current conservation program (R: F). Furthermore, this study highlights the need to monitor dynamic changes in genetic diversity in conserved breeds over successive generations. Our research provides new insights into genetic diversity dynamics in conserved populations, and lays a solid foundation for improving conservation schemes. The online version of this article (10.1186/s12864-018-4973-6) contains supplementary material, which is available to authorized users.

Ceballos FC, Joshi PK, Clark DW, Ramsay M, Wilson JF . Runs of homozygosity: windows into population history and trait architecture
Nat Rev Genet, 2018,19(4):220-234.
URLPMID:29335644 [本文引用: 1]
Abstract Long runs of homozygosity (ROH) arise when identical haplotypes are inherited from each parent and thus a long tract of genotypes is homozygous. Cousin marriage or inbreeding gives rise to such autozygosity; however, genome-wide data reveal that ROH are universally common in human genomes even among outbred individuals. The number and length of ROH reflect individual demographic history, while the homozygosity burden can be used to investigate the genetic architecture of complex disease. We discuss how to identify ROH in genome-wide microarray and sequence data, their distribution in human populations and their application to the understanding of inbreeding depression and disease risk.

Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MA, Bender D, Maller J, Sklar P, de Bakker PI, Daly MJ, Sham PC . PLINK: a tool set for whole-genome association and population-based linkage analyses
Am J Hum Genet, 2007,81(3):559-75.
URL [本文引用: 1]

Gusev A, Lowe JK, Stoffel M, Daly MJ, Altshuler D, Breslow JL, Friedman JM, Pe'er I . Whole population, genome-wide mapping of hidden relatedness
Genome Res, 2009,19(2):318-26.
[本文引用: 1]

Zhang L, Orloff MS, Reber S, Li S, Zhao Y, Eng C . CgaTOH: extended approach for identifying tracts of homozygosity
PLoS One, 2013,8(3):e57772.
URLPMID:23469237 [本文引用: 1]
Identification of disease variants via homozygosity mapping and investigation of the effects of genome-wide homozygosity regions on traits of biomedical importance have been widely applied recently. Nonetheless, the existing methods and algorithms to identify long tracts of homozygosity (TOH) are not able to provide efficient and rigorous regions for further downstream association investigation. We expanded current methods to identify TOHs by defining urrogate-TOH , a region covering a cluster of TOHs with specific characteristics. Our defined surrogate-TOH includes cTOH, viz a common TOH region where at least ten TOHs present; gTOH, whereby a group of highly overlapping TOHs share proximal boundaries; and aTOH, which are allelically-matched TOHs. Searching for gTOH and aTOH was based on a repeated binary spectral clustering algorithm, where a hierarchy of clusters is created and represented by a TOH cluster tree. Based on the proposed method of identifying different species of surrogate-TOH, our cgaTOH software was developed. The software provides an intuitive and interactive visualization tool for better investigation of the high-throughput output with special interactive navigation rings, which will find its applicability in both conventional association studies and more sophisticated downstream analyses. NCBI genome map viewer is incorporated into the system. Moreover, we discuss the choice of implementing appropriate empirical ranges of critical parameters by applying to disease models. This method identifies various patterned clusters of SNPs demonstrating extended homozygosity, thus one can observe different aspects of the multi-faceted characteristics of TOHs.

Howrigan DP, Simonson MA, Keller MC . Detecting autozygosity through runs of homozygosity: a comparison of three autozygositydetection algorithms
BMC Genomics, 2011,12:460.
URL [本文引用: 1]

Browning BL, Browning SR . Detecting identity by descent and estimating genotype error rates in sequence data
Am J Hum Genet, 2013,93(5):840-51.
URLPMID:24207118 [本文引用: 1]
Existing methods for identity by descent (IBD) segment detection were designed for SNP array data, not sequence data. Sequence data have a much higher density of genetic variants and a different allele frequency distribution, and can have higher genotype error rates. Consequently, best practices for IBD detection in SNP array data do not necessarily carry over to sequence data. We present a method, IBDseq, for detecting IBD segments in sequence data and a method, SEQERR, for estimating genotype error rates at low-frequency variants by using detected IBD. The IBDseq method estimates probabilities of genotypes observed with error for each pair of individuals under IBD and non-IBD models. The ratio of estimated probabilities under the two models gives a LOD score for IBD. We evaluate several IBD detection methods that are fast enough for application to sequence data (IBDseq, Beagle Refined IBD, PLINK, and GERMLINE) under multiple parameter settings, and we show that IBDseq achieves high power and accuracy for IBD detection in sequence data. The SEQERR method estimates genotype error rates by comparing observed and expected rates of pairs of homozygote and heterozygote genotypes at low-frequency variants in IBD segments. We demonstrate the accuracy of SEQERR in simulated data, and we apply the method to estimate genotype error rates in sequence data from the UK10K and 1000 Genomes projects.

Magi A, Tattini L, Palombo F, Benelli M, Gialluisi A, Giusti B, Abbate R, Seri M, Gensini GF, Romeo G, Pippucci T . H3M2: detection of runs of homozygosity from whole-exome sequencing data
Bioinformatics, 2014,30(20):2852-2859.
URLPMID:24966365 [本文引用: 1]
Runs of homozygosity (ROH) are sizable chromosomal stretches of homozygous genotypes, ranging in length from tens of kilobases to megabases. ROHs can be relevant for population and medical genetics, playing a role in predisposition to both rare and common disorders. ROHs are commonly detected by single nucleotide polymorphism (SNP) microarrays, but attempts have been made to use whole-exome sequencing (WES) data. Currently available methods developed for the analysis of uniformly spaced SNP-array maps do not fit easily to the analysis of the sparse and non-uniform distribution of the WES target design.To meet the need of an approach specifically tailored to WES data, we developed [Formula: see text], an original algorithm based on heterogeneous hidden Markov model that incorporates inter-marker distances to detect ROH from WES data. We evaluated the performance of [Formula: see text] to correctly identify ROHs on synthetic chromosomes and examined its accuracy in detecting ROHs of different length (short, medium and long) from real 1000 genomes project data. [Formula: see text] turned out to be more accurate than GERMLINE and PLINK, two state-of-the-art algorithms, especially in the detection of short and medium ROHs.[Formula: see text] is a collection of bash, R and Fortran scripts and codes and is freely available at https://sourceforge.net/projects/h3m2/.albertomagi@gmail.comSupplementary data are available at Bioinformatics online.

Vigeland MD, Gjøtterud KS, Selmer KK . FILTUS: a desktop GUI for fast and efficient detection of disease- causing variants, including a novel autozygosity detector
Bioinformatics, 2016,32(10):1592-1594.
URL [本文引用: 1]

Narasimhan V, Danecek P, Scally A, Xue Y, Tyler-Smith C, Durbin R . BCFtools/RoH: a hidden Markov model approach for detecting autozygosity from next-generation sequencing data
Bioinformatics, 2016,32(11):1749-1751.
URLPMID:4892413 [本文引用: 1]
Summary:Runs of homozygosity (RoHs) are genomic stretches of a diploid genome that show identical alleles on both chromosomes. Longer RoHs are unlikely to have arisen by chance but are likely to denote autozygosity, whereby both copies of the genome descend from the same recent ancestor. Early tools to detect RoH used genotype array data, but substantially more information is available from sequencing data. Here, we present and evaluate BCFtools/RoH, an extension to the BCFtools software package, that detects regions of autozygosity in sequencing data, in particular exome data, using a hidden Markov model. By applying it to simulated data and real data from the 1000 Genomes Project we estimate its accuracy and show that it has higher sensitivity and specificity than existing methods under a range of sequencing error rates and levels of autozygosity. Availability and implementation: BCFtools/RoH and its associated binary/source files are freely available fromhttps://github.com/samtools/BCFtools. Contact:vn2@sanger.ac.ukorpd3@sanger.ac.uk Supplementary information:Supplementary dataare available atBioinformaticsonline.

Szpiech ZA, Blant A, Pemberton TJ . GARLIC: Genomic Autozygosity Regions Likelihood-based Inference and Classification
Bioinformatics, 2017,33(13):2059-2062.
URLPMID:28205676 [本文引用: 1]
Abstract Summary: Runs of homozygosity (ROH) are important genomic features that manifest when identical-by-descent haplotypes are inherited from parents. Their length distributions and genomic locations are informative about population history and they are useful for mapping recessive loci contributing to both Mendelian and complex disease risk. Here, we present software implementing a model-based method ( Pemberton et al., 2012 ) for inferring ROH in genome-wide SNP datasets that incorporates population-specific parameters and a genotyping error rate as well as provides a length-based classification module to identify biologically interesting classes of ROH. Using simulations, we evaluate the performance of this method. Availability and Implementation: GARLIC is written in C ++. Source code and pre-compiled binaries (Windows, OSX and Linux) are hosted on GitHub ( https://github.com/szpiech/garlic ) under the GNU General Public License version 3. Contact: zachary.szpiech@ucsf.edu. Supplementary information: Supplementary data are available at Bioinformatics online. The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

Bjelland DW, Weigel KA, Vukasinovic N, Nkrumah JD . Evaluation of inbreeding depression in Holstein cattle using whole-genome SNP markers and alternative measures of genomic inbreeding
J Dairy Sci, 2013,96(7):4697-4706.
URLPMID:23684028
The effects of increased pedigree inbreeding in dairy cattle populations have been well documented and result in a negative impact on profitability. Recent advances in genotyping technology have allowed researchers to move beyond pedigree analysis and study inbreeding at a molecular level. In this study, 5,853 animals were genotyped for 54,001 single nucleotide polymorphisms (SNP); 2,913 cows had phenotypic records including a single lactation for milk yield (from either lactation 1, 2, 3, or 4), reproductive performance, and linear type conformation. After removing SNP with poor call rates, low minor allele frequencies, and departure from Hardy-Weinberg equilibrium, 33,025 SNP remained for analyses. Three measures of genomic inbreeding were evaluated: percent homozygosity (FPH), inbreeding calculated from runs of homozygosity (FROH), and inbreeding derived from a genomic relationship matrix (FGRM). Average FPHwas 60.5±1.1%, average FROHwas 3.8±2.1%, and average FGRMwas 20.8±2.3%, where animals with larger values for each of the genomic inbreeding indices were considered more inbred. Decreases in total milk yield to 205d postpartum of 53, 20, and 47kg per 1% increase in FPH, FROH, and FGRM, respectively, were observed. Increases in days open per 1% increase in FPH(1.76 d), FROH(1.72 d), and FGRM(1.06 d) were also noted, as well as increases in maternal calving difficulty (0.09, 0.03, and 0.04 on a 5-point scale for FPH, FROH, and FGRM, respectively). Several linear type traits, such as strength (610.40, 610.11, and 610.19), rear legs rear view (610.35, 610.16, and 610.14), front teat placement (0.35, 0.25, 0.18), and teat length (610.24, 610.14, and 610.13) were also affected by increases in FPH, FROH, and FGRM, respectively. Overall, increases in each measure of genomic inbreeding in this study were associated with negative effects on production and reproductive ability in dairy cows.

Biscarini F, Biffani S, Nicolazzi EL, Morandi N, Stella A. Applying runs of homozygosity to the detection of associations between genotype and phenotype in farm animals
In:Proceedings of the 10th World Congress of Genetics Applied to Livestock Production. Vancouver, BC, Canada, 2014.


Scraggs E, Zanella R, Wojtowicz A, Taylor JF, Gaskins CT, Reeves JJ, de Avila JM, Neibergs HL . Estimation of inbreeding and effective population size of full-blood Wagyu cattle registered with the American Wagyu Cattle Association
J Anim Breed Genet, 2014,131(1):3-10.
URLPMID:24373025
SummaryThe objective of this research was to examine the population structure of full-blood (100%) Wagyu cattle registered in the United States with the American Wagyu Association, with the aim of estimating and comparing the levels of inbreeding from both pedigree and genotypic data. A total of 4132 full-blood Wagyu cattle pedigrees were assessed and used to compute the inbreeding coefficients (FIT and FST) and the effective population size (Ne) from pedigree data for the period 1994 to 2011. In addition to pedigree analysis, 47 full-blood Wagyu cattle representing eight prominent sire lines in the American Wagyu cattle population were genotyped using the Illumina BovineSNP50 BeadChip. Genotypic data were then used to estimate genomic inbreeding coefficients (FROH) by calculating runs of homozygosity. The mean inbreeding coefficient based on the pedigree data was estimated at 4.80%. The effective population size averaged 17 between the years 1994 and 2011 with an increase of 42.9 in 2000 and a drop of 1.8 in 2011. Examination of the runs of homozygosity revealed that the 47 Wagyu cattle from the eight prominent sire lines had a mean genomic inbreeding coefficient (FROH) estimated at 9.08% compared to a mean inbreeding coefficient based on pedigree data of 4.8%. These data suggest that the mean genotype inbreeding coefficient of full-blood Wagyu cattle exceeds the inbreeding coefficient identified by pedigree. Inbreeding has increased slowly at a rate of 0.03% per year over the past 17 years. Wagyu breeders should continue to utilize many sires from divergent lines and consider outcrossing to other breeds to enhance genetic diversity and minimize the adverse effects of inbreeding in Wagyu.

Mészáros G, Boison SA, Pérez O'Brien AM, Ferencaković M, Curik I, Da Silva MV, Utsunomiya YT, Garcia JF, Sölkner J . Genomic analysis for managing small and endangered populations: a case study in Tyrol Grey cattle
Front Genet, 2015,6:173.
URLPMID:4443735 [本文引用: 1]
Abstract Analysis of genomic data is increasingly becoming part of the livestock industry. Therefore, the routine collection of genomic information would be an invaluable resource for effective management of breeding programs in small, endangered populations. The objective of the paper was to demonstrate how genomic data could be used to analyse (1) linkage disequlibrium (LD), LD decay and the effective population size (NeLD); (2) Inbreeding level and effective population size (NeROH) based on runs of homozygosity (ROH); (3) Prediction of genomic breeding values (GEBV) using small within-breed and genomic information from other breeds. The Tyrol Grey population was used as an example, with the goal to highlight the potential of genomic analyses for small breeds. In addition to our own results we discuss additional use of genomics to assess relatedness, admixture proportions, and inheritance of harmful variants. The example data set consisted of 218 Tyrol Grey bull genotypes, which were all available AI bulls in the population. After standard quality control restrictions 34,581 SNPs remained for the analysis. A separate quality control was applied to determine ROH levels based on Illumina GenCall and Illumina GenTrain scores, resulting into 211 bulls and 33,604 SNPs. LD was computed as the squared correlation coefficient between SNPs within a 10 mega base pair (Mb) region. ROHs were derived based on regions covering at least 4, 8, and 16 Mb, suggesting that animals had common ancestors approximately 12, 6, and 3 generations ago, respectively. The corresponding mean inbreeding coefficients (F ROH) were 4.0% for 4 Mb, 2.9% for 8 Mb and 1.6% for 16 Mb runs. With an average generation interval of 5.66 years, estimated NeROH was 125 (NeROH>16 Mb), 186 (NeROH>8 Mb) and 370 (NeROH>4 Mb) indicating strict avoidance of close inbreeding in the population. The LD was used as an alternative method to infer the population history and the Ne. The results show a continuous decrease in NeLD, to 780, 120, and 80 for 100, 10, and 5 generations ago, respectively. Genomic selection was developed for and is working well in large breeds. The same methodology was applied in Tyrol Grey cattle, using different reference populations. Contrary to the expectations, the accuracy of GEBVs with very small within breed reference populations were very high, between 0.13-0.91 and 0.12-0.63, when estimated breeding values and deregressed breeding values were used as pseudo-phenotypes, respectively. Subsequent analyses confirmed the high accuracies being a consequence of low reliabilities of pseudo-phenotypes in the validation set, thus being heavily influenced by parent averages. Multi-breed and across breed reference sets gave inconsistent and lower accuracies. Genomic information may have a crucial role in management of small breeds, even if its primary usage differs from that of large breeds. It allows to assess relatedness between individuals, trends in inbreeding and to take decisions accordingly. These decisions would be based on the real genome architecture, rather than conventional pedigree information, which can be missing or incomplete. We strongly suggest the routine genotyping of all individuals that belong to a small breed in order to facilitate the effective management of endangered livestock populations.

Williams JL, Hall SJ, Del Corvo M, Ballingall KT, Colli L, Ajmone Marsan P, Biscarini F . Inbreeding and purging at the genomic Level: the Chillingham cattle reveal extensive, non-random SNP heterozygosity
Anim Genet, 2016,47(1):19-27.
URLPMID:26559490 [本文引用: 1]
Summary Local breeds of livestock are of conservation significance as components of global biodiversity and as reservoirs of genetic variation relevant to the future sustainability of agriculture. One such rare historic breed, the Chillingham cattle of northern England, has a 350-year history of isolation and inbreeding yet shows no diminution of viability or fertility. The Chillingham cattle have not been subjected to selective breeding. It has been suggested previously that the herd has minimal genetic variation. In this study, high-density SNP genotyping with the 777K SNP chip showed that 9.1% of loci on the chip are polymorphic in the herd, compared with 62–90% seen in commercial cattle breeds. Instead of being homogeneously distributed along the genome, these loci are clustered at specific chromosomal locations. A high proportion of the Chillingham individuals examined were heterozygous at many of these polymorphic loci, suggesting that some loci are under balancing selection. Some of these frequently heterozygous loci have been implicated as sites of recessive lethal mutations in cattle. Linkage disequilibrium equal or close to 100% was found to span up to 135002kb, and LD was above r 202=020.25 up to more than 500002kb. This strong LD is consistent with the lack of polymorphic loci in the herd. The heterozygous regions in the Chillingham cattle may be the locations of genes relevant to fitness or survival, which may help elucidate the biology of local adaptation in traditional breeds and facilitate selection for such traits in commercial cattle.

Zavarez LB, Utsunomiya YT, Carmo AS, Neves HH, Carvalheiro R, Ferencaković M, Pérez O'Brien AM, Curik I, Cole JB, Van Tassell CP, da Silva MV, Sonstegard TS, Sölkner J, Garcia JF . Assessment of autozygosity in Nellore cows (Bos indicus) through high-density SNP genotypes
Front Genet, 2015,6:5.


Kim ES, Sonstegard TS, Rothschild MF . Recent artificial selection in U.S. Jersey cattle impacts autozygosity levels of specific genomic regions
BMC Genomics, 2015,16:302.
URLPMID:4409734
Background Genome signatures of artificial selection in U.S. Jersey cattle were identified by examining changes in haplotype homozygosity for a resource population of animals born between 1953 and...

Iacolina L, Stronen AV, Pertoldi C, Tokarska M, Nørgaard LS, Muñoz J, Kjærsgaard A, Ruiz-Gonzalez A, Kamiński S, Purfield DC . Novel graphical analyses of runs of homozygosity among species and livestock breeds
Int J Genomics, 2016,2152847.


Peripolli E, Stafuzza NB, Munari DP, Lima ALF, Irgang R, Machado MA, Panetto JCDC, Ventura RV, Baldi F, da Silva MVGB . Assessment of runs of homozygosity islands and estimates of genomic inbreeding in Gyr (Bos indicus) dairy cattle
BMC Genomics, 2018,19:34.
URLPMID:29316879 [本文引用: 3]
Runs of homozygosity (ROH) are continuous homozygous segments of the DNA sequence. They have been applied to quantify individual autozygosity and used as a potential inbreeding measure in livestock species. The aim of the present study was (i) to investigate genome-wide autozygosity to identify and characterize ROH patterns in Gyr dairy cattle genome; (ii) identify ROH islands for gene content and enrichment in segments shared by more than 50% of the samples, and (iii) compare estimates of molecular inbreeding calculated from ROH (FROH), genomic relationship matrix approach (FGRM) and based on the observed versus expected number of homozygous genotypes (FHOM), and from pedigree-based coefficient (FPED). ROH were identified in all animals, with an average number of 55.1265±6510.37 segments and a mean length of 3.1702Mb. Short segments (ROH1–2 Mb) were abundant through the genomes, which accounted for 60% of all segments identified, even though the proportion of the genome covered by them was relatively small. The findings obtained in this study suggest that on average 7.01% (175.2802Mb) of the genome of this population is autozygous. Overlapping ROH were evident across the genomes and 14 regions were identified with ROH frequencies exceeding 50% of the whole population. Genes associated with lactation (TRAPPC9), milk yield and composition(IRS2andANG), and heat adaptation (HSF1,HSPB1,andHSPE1), were identified. Inbreeding coefficients were estimated through the application of FROH, FGRM, FHOM, and FPEDapproaches. FPEDestimates ranged from 0.00 to 0.327 and FROHfrom 0.001 to 0.201. Low to moderate correlations were observed between FPED-FROHand FGRM-FROH, with values ranging from 610.11 to 0.51. Low to high correlations were observed between FROH-FHOMand moderate between FPED-FHOMand FGRM-FHOM. Correlations between FROHfrom different lengths and FPEDgradually increased with ROH length. Genes inside ROH islands suggest a strong selection for dairy traits and enrichment for Gyr cattle environmental adaptation. Furthermore, low FPED-FROHcorrelations for small segments indicate that FPEDestimates are not the most suitable method to capture ancient inbreeding. The existence of a moderate correlation between larger ROH indicates that FROHcan be used as an alternative to inbreeding estimates in the absence of pedigree records. The online version of this article (10.1186/s12864-017-4365-3) contains supplementary material, which is available to authorized users.

Forutan M, Ansari Mahyari S, Baes C, Melzer N, Schenkel FS, Sargolzaei M . Inbreeding and runs of homozygosity before and after genomic selection in North American Holstein cattle
BMC Genomics, 2018,19(1):98.
URLPMID:29374456
While autozygosity as a consequence of selection is well understood, there is limited information on the ability of different methods to measure true inbreeding. In the present study, a gene dropping simulation was performed and inbreeding estimates based on runs of homozygosity (ROH), pedigree, and the genomic relationship matrix were compared to true inbreeding. Inbreeding based on ROH was estimated using SNP1101, PLINK, and BCFtools software with different threshold parameters. The effects of different selection methods on ROH patterns were also compared. Furthermore, inbreeding coefficients were estimated in a sample of genotyped North American Holstein animals born from 1990 to 2016 using 50 k chip data and ROH patterns were assessed before and after genomic selection. Using ROH with a minimum window size of 20 to 50 using SNP1101 provided the closest estimates to true inbreeding in simulation study. Pedigree inbreeding tended to underestimate true inbreeding, and results for genomic inbreeding varied depending on assumptions about base allele frequencies. Using an ROH approach also made it possible to assess the effect of population structure and selection on distribution of runs of autozygosity across the genome. In the simulation, the longest individual ROH and the largest average length of ROH were observed when selection was based on best linear unbiased prediction (BLUP), whereas genomic selection showed the largest number of small ROH compared to BLUP estimated breeding values (BLUP-EBV). In North American Holsteins, the average number of ROH segments of 1 Mb or more per individual increased from 57 in 1990 to 82 in 2016. The rate of increase in the last 5 years was almost double that of previous 5 year periods. Genomic selection results in less autozygosity per generation, but more per year given the reduced generation interval. This study shows that existing software based on the measurement of ROH can accurately identify autozygosity across the genome, provided appropriate threshold parameters are used. Our results show how different selection strategies affect the distribution of ROH, and how the distribution of ROH has changed in the North American dairy cattle population over the last 25 years. The online version of this article (10.1186/s12864-018-4453-z) contains supplementary material, which is available to authorized users.

Kim K, Jung J, Caetano-Anollés K, Sung S, Yoo D, Choi BH, Kim HC, Jeong JY, Cho YM, Park EW, Choi TJ, Park B, Lim D, Kim H . Artificial selection increased body weight but induced increase of runs of homozygosity in Hanwoo cattle
PLoS One, 2018,13(3):e0193701.
URL [本文引用: 3]

Mukherjee A, Mukherjee S, Dhakal R, Mech M, Longkumer I, Haque N, Vupru K, Khate K, Jamir IY, Pongen P, Rajkhowa C, Mitra A, Guldbrandtsen B, Sahana G . High- density genotyping reveals genomic characterization, population structure and genetic diversity of indian Mithun (Bos frontalis)
Sci Rep, 2018,8(1):10316.
URLPMID:29985484
The current study aimed at genomic characterization and improved understanding of genetic diversity of two Indian mithun populations (both farm, 48 animals and field, 24 animals) using genome wide genotype data generated with Illumina BovineHD BeadChip. Eight additional populations of taurine cattle (Holstein and NDama), indicine cattle (Gir) and other evolutionarily closely related species (Bali cattle, Yak, Bison, Gaur and wild buffalo) were also included in this analysis (N = 137) for comparative purposes. Our results show that the genetic background of mithun populations was uniform with few possible signs of indicine admixture. In general, observed and expected heterozygosities were quite similar in these two populations. We also observed increased frequencies of small-sized runs of homozygosity (ROH) in the farm population compared to field mithuns. On the other hand, longer ROH were more frequent in field mithuns, which suggests recent founder effects and subsequent genetic drift due to close breeding in farmer herds. This represents the first study providing genetic evidence about the population structure and genomic diversity of Indian mithun. The information generated will be utilized for devising suitable breeding and conservation programme for mithun, an endangered bovine species in India.

Goszczynski D, Molina A, Terán E, Morales-Durand H, Ross P, Cheng H, Giovambattista G, Demyda-Peyrás S . Runs of homozygosity in a selected cattle population with extremely inbred bulls: descriptive and functional analyses revealed highly variable patterns
PLoS One, 2018,13(7):e0200069.
URLPMID:29985951
The analysis of runs of homozygosity (ROH), using high throughput genomic data, has become a valuable and frequently used methodology to characterize the genomic and inbreeding variation of livestock and wildlife animal populations. However, this methodology has been scarcely used in highly inbred domestic animals. Here, we analyzed and characterized the occurrence of ROH fragments in highly inbred (HI; average pedigree-based inbreeding coefficient FPED= 0.164; 0.103 to 0.306) and outbred Retinta bulls (LI; average FPED= 0.008; 0 to 0.025). We studied the length of the fragments, their abundance, and genome distribution using high-density microarray data. The number of ROH was significantly higher in the HI group, especially for long fragments (>8Mb). In the LI group, the number of ROH continuously decreased with fragment length. Genome-wide distribution of ROH was highly variable between samples. Some chromosomes presented a larger number of fragments (BTA1, BTA19, BTA29), others had longer fragments (BTA4, BTA12, BTA17), while other ones showed an increased ROH accumulation over specific loci (BTA2, BTA7, BTA23, BTA29). Similar differences were observed in the analysis of 12 individuals produced by a similar inbred event (FPED3= 0.125). The correlation between the fraction of the genome covered by ROH (FROH) and FPEDwas high (0.79), suggesting that ROH-based estimations are indicative of inbreeding levels. On the other hand, the correlation between FPEDand the microsatellite-based inbreeding coefficient (FMIC) was only moderate (r = 0.44), suggesting that STR-based inbreeding estimations should be avoided. Similarly, we found a very low correlation (r = -0.0132) between recombination rate and ROH abundance across the genome. Finally, we performed functional annotation analyses of genome regions with significantly enriched ROH abundance. Results revealed gene clusters related to pregnancy-associated proteins and immune reaction. The same analysis performed for regions enriched with recently formed ROH (> 8 Mb) showed gene clusters related to flagellum assembly. In both cases, the processes were related to male and female reproductive functions, which may partially explain the reduced fertility associated with inbred populations.

Nandolo W, Utsunomiya YT, Mészáros G, Wurzinger M, Khayadzadeh N, Torrecilha RBP, Mulindwa HA, Gondwe TN, Waldmann P, Ferencaković M, Garcia JF, Rosen BD, Bickhart D, van Tassell CP, Curik I, Sölkner J . Misidentification of runs of homozygosity islands in cattle caused by interference with copy number variation or large intermarker distances
Genet Sel Evol, 2018,50:43.


Ai H, Huang L, Ren J . Genetic diversity, linkage disequilibrium and selection signatures in chinese and Western pigs revealed by genome-wide SNP markers
PLoS One, 2013,8(2):e56001.
URL

Silió L, Rodríguez MC, Fernández A, Barragán C, Benítez R, óvilo C, Fernández AI . Measuring inbreeding and inbreeding depression on pig growth from pedigree or SNP-derived metrics
J Anim Breed Genet, 2013,130(5):349-360.
URLPMID:24074172 [本文引用: 1]
SummaryMultilocus homozygosity, measured as the proportion of the autosomal genome in homozygous genotypes or in runs of homozygosity, was compared with the respective pedigree inbreeding coefficients in 64 Iberian pigs genotyped using the Porcine SNP60 Beadchip. Pigs were sampled from a set of experimental animals with a large inbreeding variation born in a closed strain with a completely recorded multi-generation genealogy. Individual inbreeding coefficients calculated from pedigree were strongly correlated with the different SNP-derived metrics of homozygosity (r02=020.814–0.919). However, unequal correlations between molecular and pedigree inbreeding were observed at chromosomal level being mainly dependent on the number of SNPs and on the correlation between heterozygosities measured across different loci. A panel of 192 SNPs of intermediate frequencies was selected for genotyping 322 piglets to test inbreeding depression on postweaning growth performance (daily gain and weight at 9002days). The negative effects on these traits of homozygosities calculated from the genotypes of 168 quality-checked SNPs were similar to those of inbreeding coefficients. The results support that few hundreds of SNPs may be useful for measuring inbreeding and inbreeding depression, when the population structure or the mating system causes a large variance of inbreeding.

Zanella R, Peixoto JO, Cardoso FF, Cardoso LL, Biegelmeyer P, Cantão ME, Otaviano A, Freitas MS, Caetano AR, Ledur MC . Genetic diversity analysis of two commercial breeds of pigs using genomic and pedigree data
Genet Sel Evol, 2016,48:24.
URL

Grossi DA, Jafarikia M, Brito LF, Buzanskas ME, Sargolzaei M, Schenkel FS . Genetic diversity, extent of linkage disequilibrium and persistence of gametic phase in Canadian pigs
BMC Genet, 2017,18(1):6.
[本文引用: 1]

Yang B, Cui L, Perez-Enciso M, Traspov A, Crooijmans RPMA, Zinovieva N, Schook LB, Archibald A, Gatphayak K, Knorr C, Triantafyllidis A, Alexandri P, Semiadi G, Hanotte O, Dias D, Dovc P, Uimari P, Iacolina L, Scandura M, Groenen MAM, Huang L, Megens HJ . Genome-wide SNP data unveils the globalization of domesticated pigs
Genet Sel Evol, 2017,49:71.
URLPMID:5609043
Abstract Background Pigs were domesticated independently in Eastern and Western Eurasia early during the agricultural revolution, and have since been transported and traded across the globe. Here, we present a worldwide survey on 60K genome-wide single nucleotide polymorphism (SNP) data for 2093 pigs, including 1839 domestic pigs representing 122 local and commercial breeds, 215 wild boars, and 39 out-group suids, from Asia, Europe, America, Oceania and Africa. The aim of this study was to infer global patterns in pig domestication and diversity related to demography, migration, and selection. Results A deep phylogeographic division reflects the dichotomy between early domestication centers. In the core Eastern and Western domestication regions, Chinese pigs show differentiation between breeds due to geographic isolation, whereas this is less pronounced in European pigs. The inferred European origin of pigs in the Americas, Africa, and Australia reflects European expansion during the sixteenth to nineteenth centuries. Human-mediated introgression, which is due, in particular, to importing Chinese pigs into the UK during the eighteenth and nineteenth centuries, played an important role in the formation of modern pig breeds. Inbreeding levels vary markedly between populations, from almost no runs of homozygosity (ROH) in a number of Asian wild boar populations, to up to 20% of the genome covered by ROH in a number of Southern European breeds. Commercial populations show moderate ROH statistics. For domesticated pigs and wild boars in Asia and Europe, we identified highly differentiated loci that include candidate genes related to muscle and body development, central nervous system, reproduction, and energy balance, which are putatively under artificial selection. Conclusions Key events related to domestication, dispersal, and mixing of pigs from different regions are reflected in the 60K SNP data, including the globalization that has recently become full circle since Chinese pig breeders in the past decades started selecting Western breeds to improve local Chinese pigs. Furthermore, signatures of ongoing and past selection, acting at different times and on different genetic backgrounds, enhance our insight in the mechanism of domestication and selection. The global diversity statistics presented here highlight concerns for maintaining agrodiversity, but also provide a necessary framework for directing genetic conservation.

Lago LV, Nery da Silva A, Zanella EL, Groke Marques M, Peixoto JO, da Silva MVGB, Ledur MC, Zanella R . Identification of genetic regions associated with scrotal hernias in a commercial swine herd
Vet Sci, 2018,5(1).
URLPMID:29382056
Abstract In this paper, we have used two approaches to detect genetic associations with scrotal hernias in commercial pigs. Firstly, we have investigated the effects of runs of homozygosity (ROH) with the appearance of scrotal hernias, followed by a Genome Wide Association Study (GWAS). The phenotype classification was based on visual appearance of scrotal hernias. Each affected animal was matched to a healthy control from the same pen. In the total, 68 animals were genotyped using the Porcine SNP60 Beadchip, out of those, 41 animals had the presence of hernias and 27 were healthy animals. Fifteen animals were removed from the analysis due to differences in genetic background, leaving 18 healthy animals and 35 piglets with scrotal hernia. Further, the detection of extended haplotypes shared ROH were conducted for health (control) and affected (case) animals and a permutation test was used to test whether the ROH segments were more frequent in case/case pairs than non-case/case pairs. Using the ROH, we have identified an association ( p = 0.019) on chromosome 2(SSC2) being segregated on animals with the presence of scrotal hernias. Using a GWAS, a region composed by 3 SNPs on the sexual chromosome X (SSCX) were associated with scrotal hernias ( p < 1.6 10 -5 ), this region harbors the Androgen Receptor Gene ( AR ).

Al-Mamun HA, Clark SA, Kwan P, Gondro C . Genome- wide linkage disequilibrium and genetic diversity in five populations of Australian domestic sheep
Genet Sel Evol, 2015,47:90.
URLPMID:4659207
Abstract BACKGROUND: Knowledge of the genetic structure and overall diversity of livestock species is important to maximise the potential of genome-wide association studies and genomic prediction. Commonly used measures such as linkage disequilibrium (LD), effective population size (N e ), heterozygosity, fixation index (F ST) and runs of homozygosity (ROH) are widely used and help to improve our knowledge about genetic diversity in animal populations. The development of high-density single nucleotide polymorphism (SNP) arrays and the subsequent genotyping of large numbers of animals have greatly increased the accuracy of these population-based estimates. METHODS: In this study, we used the Illumina OvineSNP50 BeadChip array to estimate and compare LD (measured by r (2) and D'), N e , heterozygosity, F ST and ROH in five Australian sheep populations: three pure breeds, i.e., Merino (MER), Border Leicester (BL), Poll Dorset (PD) and two crossbred populations i.e. F1 crosses of Merino and Border Leicester (MxB) and MxB crossed to Poll Dorset (MxBxP). RESULTS: Compared to other livestock species, the sheep populations that were analysed in this study had low levels of LD and high levels of genetic diversity. The rate of LD decay was greater in Merino than in the other pure breeds. Over short distances (<10 kb), the levels of LD were higher in BL and PD than in MER. Similarly, BL and PD had comparatively smaller N e than MER. Observed heterozygosity in the pure breeds ranged from 0.3 in BL to 0.38 in MER. Genetic distances between breeds were modest compared to other livestock species (highest F ST = 0.063) but the genetic diversity within breeds was high. Based on ROH, two chromosomal regions showed evidence of strong recent selection. CONCLUSIONS: This study shows that there is a large range of genome diversity in Australian sheep breeds, especially in Merino sheep. The observed range of diversity will influence the design of genome-wide association studies and the results that can be obtained from them. This knowledge will also be useful to design reference populations for genomic prediction of breeding values in sheep.

Kominakis A, Hager-Theodorides AL, Saridaki A, Antonakos G, Tsiamis G . Genome-wide population structure and evolutionary history of the Frizarta dairy sheep
Animal, 2017,11(10):1680-1688.
URLPMID:28274293
<div class="abstract" data-abstract-type="normal"> In the present study, we used genomic data, generated with a medium density single nucleotide polymorphisms (SNP) array, to acquire more information on the population structure and evolutionary history of the synthetic Frizarta dairy sheep. First, two typical measures of linkage disequilibrium (LD) were estimated at various physical distances that were then used to make inferences on the effective population size at key past time points. Population structure was also assessed by both multidimensional scaling analysis and <span class='italic'>k-means clustering on the distance matrix obtained from the animals’ genomic relationships. The Wright’s fixation <span class='italic'>F <span class='sub'> <span class='italic'>ST index was also employed to assess herds’ genetic homogeneity and to indirectly estimate past migration rates. The Wright’s fixation <span class='italic'>F <span class='sub'> <span class='italic'>IS index and genomic inbreeding coefficients based on the genomic relationship matrix as well as on runs of homozygosity were also estimated. The Frizarta breed displays relatively low LD levels with <span class='italic'>r <span class='sup'>2 and <span class='italic'>|D00<span class='italic'>| equal to 0.18 and 0.50, respectively, at an average inter-marker distance of 31 kb. Linkage disequilibrium decayed rapidly by distance and persisted over just a few thousand base pairs. Rate of LD decay (<span class='italic'>β) varied widely among the 26 autosomes with larger values estimated for shorter chromosomes (e.g. <span class='italic'>β=0.057, for OAR6) and smaller values for longer ones (e.g. <span class='italic'>β=0.022, for OAR2). The inferred effective population size at the beginning of the breed’s formation was as high as 549, was then reduced to 463 in 1981 (end of the breed’s formation) and further declined to 187, one generation ago. Multidimensional scaling analysis and <span class='italic'>k-means clustering suggested a genetically homogenous population, <span class='italic'>F <span class='sub'> <span class='italic'>ST estimates indicated relatively low genetic differentiation between herds, whereas a heat map of the animals’ genomic kinship relationships revealed a stratified population, at a herd level. Estimates of genomic inbreeding coefficients suggested that most recent parental relatedness may have been a major determinant of the current effective population size. A denser than the 50k SNP panel may be more beneficial when performing genome wide association studies in the breed.

Mastrangelo S, Portolano B, Di Gerlando R, Ciampolini R, Tolone M, Sardina MT , International Sheep Genomics Consortium. Genome-wide analysis in endangered populations: a case study in Barbaresca sheep
Animal, 2017,11(7):1107-1116.
URL

Zhang M, Peng WF, Hu XJ, Zhao YX, Lv FH, Yang J . Global genomic diversity and conservation priorities for domestic animals are associated with the economies of their regions of origin
Sci Rep, 2018,8(1):11677.
URL
Domestic animals play a key role in human survival and the development of civilization. However, the genetic resources of domestic animals are facing an alarming rate of erosion due to socioeconomic changes, economic globalization and financial constraints. In this study, through genome-wide SNP analysis, we estimated the heterozygosity, inbreeding coefficient, effective population size, and runs of homozygosity to identify the breeds facing the risk of extinction for sheep and cattle across the world. In particular, we quantified the contribution of 97 sheep breeds and 53 cattle breeds to genomic diversity (within-breed, between-breed and total) and prioritized the breeds for conservation. Additionally, we compared the average values of genomic diversity between breeds from regions (or countries) in different economic categories (underdeveloped, developing and developed), and found that breeds in developed regions exhibit significantly higher levels of total genomic diversity than those in underdeveloped and developing regions. Altogether, our results suggested that conservation priority should be given to breeds in developed regions to secure the future genomic diversity hotspots of domestic animal resources.

Brito LF, Kijas JW, Ventura RV, Sargolzaei M, Porto-Neto LR, Cánovas A, Feng Z, Jafarikia M, Schenkel FS . Genetic diversity and signatures of selection in various goat breeds revealed by genome-wide SNP markers
BMC Genomics, 2017,18(1):229.
URL [本文引用: 1]

Grossen C, Biebach I, Angelone-Alasaad S, Keller LF, Croll D . Population genomics analyses of European ibex species show lower diversity and higher inbreeding in reintroduced populations
Evol Appl, 2018,11(2):123-139.
URLPMID:29387150
Restoration of lost species ranges to their native distribution is key for the survival of endangered species. However, reintroductions often fail and long erm genetic consequences are poorly understood. Alpine ibex (Capra ibex) are wild goats that recovered from <100 individuals to ~50,000 within a century by population reintroductions. We analyzed the population genomic consequences of the Alpine ibex reintroduction strategy. We genotyped 101,822 genomewide single nucleotide polymorphism loci in 173 Alpine ibex, the closely related Iberian ibex (Capra pyrenaica) and domestic goat (Capra hircus). The source population of all Alpine ibex maintained genetic diversity comparable to Iberian ibex, which experienced less severe bottlenecks. All reintroduced Alpine ibex populations had individually and combined lower levels of genetic diversity than the source population. The reintroduction strategy consisted of primary reintroductions from captive breeding and secondary reintroductions from established populations. This stepwise reintroduction strategy left a strong genomic footprint of population differentiation, which increased with subsequent rounds of reintroductions. Furthermore, analyses of genomewide runs of homozygosity showed recent inbreeding primarily in individuals of reintroduced populations. We showed that despite the rapid census recovery, Alpine ibex carry a persistent genomic signature of their reintroduction history. We discuss how genomic monitoring can serve as an early indicator of inbreeding.

Zavarez LB, Utsunomiya YT, Carmo AS, Neves HH, Carvalheiro R, Ferencaković M, Pérez O'Brien AM, Curik I, Cole JB, Van Tassell CP, da Silva MV, Sonstegard TS, Sölkner J, Garcia JF . Assessment of autozygosity in Nellore cows (Bos indicus) through high-density SNP genotypes
Front Genet, 2015,6:5.
[本文引用: 1]

Visscher PM, Medland SE, Ferreira MA, Morley KI, Zhu G, Cornes BK, Montgomery GW, Martin NG . Assumption- free estimation of heritability from genome-wide identity- by-descent sharing between full siblings
PLoS Genet, 2006,2(3):e41.
URL [本文引用: 1]

Peripolli E, Munari DP, Silva MVGB, Lima ALF, Irgang R, Baldi F . Runs of homozygosity: current knowledge and applications in livestock
Anim Genet, 2017,48(3):255-271.
URLPMID:27910110 [本文引用: 2]
Abstract This review presents a broader approach to the implementation and study of runs of homozygosity (ROH) in animal populations, focusing on identifying and characterizing ROH and their practical implications. ROH are continuous homozygous segments that are common in individuals and populations. The ability of these homozygous segments to give insight into a population's genetic events makes them a useful tool that can provide information about the demographic evolution of a population over time. Furthermore, ROH provide useful information about the genetic relatedness among individuals, helping to minimize the inbreeding rate and also helping to expose deleterious variants in the genome. The frequency, size and distribution of ROH in the genome are influenced by factors such as natural and artificial selection, recombination, linkage disequilibrium, population structure, mutation rate and inbreeding level. Calculating the inbreeding coefficient from molecular information from ROH (FROH) is more accurate for estimating autozygosity and for detecting both past and more recent inbreeding effects than are estimates from pedigree data (FPED). The better results of FROH suggest that FROH can be used to infer information about the history and inbreeding levels of a population in the absence of genealogical information. The selection of superior animals has produced large phenotypic changes and has reshaped the ROH patterns in various regions of the genome. Additionally, selection increases homozygosity around the target locus, and deleterious variants are seen to occur more frequently in ROH regions. Studies involving ROH are increasingly common and provide valuable information about how the genome's architecture can disclose a population's genetic background. By revealing the molecular changes in populations over time, genome-wide information is crucial to understanding antecedent genome architecture and, therefore, to maintaining diversity and fitness in endangered livestock breeds.

Mastrangelo S, Tolone M, Di Gerlando R, Fontanesi L, Sardina MT, Portolano B . Genomic inbreeding estimation in small populations: evaluation of runs of homozygosity in three local dairy cattle breeds
Animal, 2016,10(5):746-754.
URLPMID:27076405
In the local breeds with small population size, one of the most important problems is the increase of inbreeding coefficient (F). High levels of inbreeding lead to reduced genetic diversity and inbreeding depression. The availability of high-density single nucleotide polymorphism (SNP) arrays has facilitated the quantification ofFby genomic markers in farm animals. Runs of homozygosity (ROH) are contiguous lengths of homozygous genotypes and represent an estimate of the degree of autozygosity at genome-wide level. The current study aims to quantify the genomicFderived from ROH (FROH) in three local dairy cattle breeds.FROHvalues were compared withFestimated from the genomic relationship matrix (FGRM), based on the difference between observedv. expected number of homozygous genotypes (FHOM) and the genomic homozygosity of individuali(FMOLi). The molecular coancestry coefficient (fMOLij) between individualsiandjwas also estimated. Individuals of Cinisara (71), Modicana (72) and Reggiana (168) were genotyped with the 50K v2 Illumina BeadChip. Genotypes from 96 animals of Italian Holstein cattle breed were also included in the analysis. We used a definition of ROH as tracts of homozygous genotypes that were >4 Mb. Among breeds, 3661 ROH were identified. Modicana showed the highest mean number of ROH per individual and the highest value ofFROH, whereas Reggiana showed the lowest ones. Differences among breeds existed for the ROH lengths. The individuals of Italian Holstein showed high number of short ROH segments, related to ancient consanguinity. Similar results showed the Reggiana with some extreme animals with segments covering 400 Mb and more of genome. Modicana and Cinisara showed similar results between them with the total length of ROH characterized by the presence of large segments. High correlation was found betweenFHOMandFROHranged from 0.83 in Reggiana to 0.95 in Cinisara and Modicana. The correlations amongFROHand other estimatedFcoefficients were generally lower ranged from 0.45 (FMOLi ROH) in Cinisara to 0.17 (FGRM ROH) in Modicana. On the basis of our results, recent inbreeding was observed in local breeds, considering that 16 Mb segments are expected to present inbreeding up to three generations ago. Our results showed the necessity of implementing conservation programs to control the rise of inbreeding and coancestry in the three Italian local dairy cattle breeds.

Yang ZC, Huang HT, Yan QX, Wang YC, Yu Y, Chen SH, Sun DX, Zhang SL, Zhang Y . Estimation of genomic inbreeding coefficients based on high-density snp markers in chinese holstein cattle
Hereditas(Beijing), 2017,39(1):416-23.
[本文引用: 1]

杨湛澄, 黄河天, 闫青霞, 王雅春, 俞英, 陈绍祜, 孙东晓, 张胜利, 张毅 . 利用高密度SNP标记分析中国荷斯坦牛基因组近交
遗传, 2017,39(1):16-23.
[本文引用: 1]

Msalya G, Kim ES, Laisser EL, Kipanyula MJ, Karimuribo ED, Kusiluka LJ, Chenyambuga SW, Rothschild MF . Determination of genetic structure and signatures of selection in three strains of tanzania shorthorn zebu, boran and friesian cattle by genome-wide snp analyses
PLoS One, 2017,12(1):e0171088.
URLPMID:28129396
Background More than 90 percent of cattle in Tanzania belong to the indigenous Tanzania Short Horn Zebu (TSZ) population which has been classified into 12 strains based on historical evidence, morphological characteristics, and geographic distribution. However, specific genetic information of each TSZ population has been lacking and has caused difficulties in designing programs such as selection, crossbreeding, breed improvement or conservation. This study was designed to evaluate the genetic structure, assess genetic relationships, and to identify signatures of selection among cattle of Tanzania with the main goal of understanding genetic relationship, variation and uniqueness among them. Methodology/Principal findings The Illumina Bos indicus SNP 80K BeadChip was used to genotype genome wide SNPs in 168 DNA samples obtained from three strains of TSZ cattle namely Maasai, Tarime and Sukuma as well as two comparative breeds; Boran and Friesian. Population structure and signatures of selection were examined using principal component analysis (PCA), admixture analysis, pairwise distances (FST), integrated haplotype score (iHS), identical by state (IBS) and runs of homozygosity (ROH). There was a low level of inbreeding (F~0.01) in the TSZ population compared to the Boran and Friesian breeds. The analyses of FST, IBS and admixture identified no considerable differentiation between TSZ trains. Importantly, common ancestry in Boran and TSZ were revealed based on admixture and IBD, implying gene flow between two populations. In addition, Friesian ancestry was found in Boran. A few common significant iHS were detected, which may reflect influence of recent selection in each breed or strain. Conclusions Population admixture and selection signatures could be applied to develop conservation plan of TSZ cattle as well as future breeding programs in East African cattle.

VanRaden PM . Efficient methods to compute genomic predictions
J Dairy Sci, 2008,91(11):4414-4423.
URLPMID:18946147 [本文引用: 1]
Efficient methods for processing genomic data were developed to increase reliability of estimated breeding values and to estimate thousands of marker effects simultaneously. Algorithms were derived and computer programs tested with simulated data for 2,967 bulls and 50,000 markers distributed randomly across 30 chromosomes. Estimation of genomic inbreeding coefficients required accurate estimates of allele frequencies in the base population. Linear model predictions of breeding values were computed by 3 equivalent methods: 1) iteration for individual allele effects followed by summation across loci to obtain estimated breeding values, 2) selection index including a genomic relationship matrix, and 3) mixed model equations including the inverse of genomic relationships. A blend of first- and second-order Jacobi iteration using 2 separate relaxation factors converged well for allele frequencies and effects. Reliability of predicted net merit for young bulls was 63% compared with 32% using the traditional relationship matrix. Nonlinear predictions were also computed using iteration on data and nonlinear regression on marker deviations; an additional (about 3%) gain in reliability for young bulls increased average reliability to 66%. Computing times increased linearly with number of genotypes. Estimation of allele frequencies required 2 processor days, and genomic predictions required <1 d per trait, and traits were processed in parallel. Information from genotyping was equivalent to about 20 daughters with phenotypic records. Actual gains may differ because the simulation did not account for linkage disequilibrium in the base population or selection in subsequent generations.

Garrod AE. Oxon MD, Lond FRCP . The incidence of alkaptonuria: a study of chemical individuality
Mol Med, 1996,2(3):274-282.
URLPMID:2588790 [本文引用: 1]
PMCID: PMC2588790

Szpiech ZA, Xu J, Pemberton TJ, Peng W, Zöllner S, Rosenberg NA, Li JZ . Long runs of homozygosity are enriched for deleterious variation
Am J Hum Genet, 2013,93(1):90-102.
URLPMID:23746547 [本文引用: 1]
Exome sequencing offers the potential to study the population-genomic variables that underlie patterns of deleterious variation. Runs of homozygosity (ROH) are long stretches of consecutive homozygous genotypes probably reflecting segments shared identically by descent as the result of processes such as consanguinity, population size reduction, and natural selection. The relationship between ROH and patterns of predicted deleterious variation can provide insight into the way in which these processes contribute to the maintenance of deleterious variants. Here, we use exome sequencing to examine ROH in relation to the distribution of deleterious variation in 27 individuals of varying levels of apparent inbreeding from 6 human populations. A significantly greater fraction of all genome-wide predicted damaging homozygotes fall in ROH than would be expected from the corresponding fraction of nondamaging homozygotes in ROH (p < 0.001). This pattern is strongest for long ROH (p < 0.05). ROH, and especially long ROH, harbor disproportionately more deleterious homozygotes than would be expected on the basis of the total ROH coverage of the genome and the genomic distribution of nondamaging homozygotes. The results accord with a hypothesis that recent inbreeding, which generates long ROH, enables rare deleterious variants to exist in homozygous form. Thus, just as inbreeding can elevate the occurrence of rare recessive diseases that represent homozygotes for strongly deleterious mutations, inbreeding magnifies the occurrence of mildly deleterious variants as well.

Huson HJ, Kim ES, Godfrey RW, Olson TA, McClure MC, Chase CC, Rizzi R, O'Brien AM, Van Tassell CP, Garcia JF, Sonstegard TS . Genome-wide association study and ancestral origins of the slick-hair coat in tropically adapted cattle
Front Genet, 2014,5:101.
[本文引用: 1]

Pryce JE, Haile-Mariam M, Goddard ME, Hayes BJ . Identification of genomic regions associated with inbreeding depression in Holstein and Jersey dairy cattle
Genet Sel Evol, 2014,46:71.
URLPMID:25407532 [本文引用: 1]
Background Inbreeding reduces the fitness of individuals by increasing the frequency of homozygous deleterious recessive alleles. Some insight into the genetic architecture of fitness, and other complex traits, can be gained by using single nucleotide polymorphism (SNP) data to identify regions of the genome which lead to reduction in performance when identical by descent (IBD). Here, we compared the effect of genome-wide and location-specific homozygosity on fertility and milk production traits in dairy cattle. Methods Genotype data from more than 43 000 SNPs were available for 8853 Holstein and 4138 Jersey dairy cows that were part of a much larger dataset that had pedigree records (338 696 Holstein and 64 049 Jersey animals). Measures of inbreeding were based on: (1) pedigree data; (2) genotypes to determine the realised proportion of the genome that is IBD; (3) the proportion of the total genome that is homozygous and (4) runs of homozygosity (ROH) which are stretches of the genome that are homozygous. Results A 1% increase in inbreeding based either on pedigree or genomic data was associated with a decrease in milk, fat and protein yields of around 0.4 to 0.6% of the phenotypic mean, and an increase in calving interval (i.e. a deterioration in fertility) of 0.02 to 0.05% of the phenotypic mean. A genome-wide association study using ROH of more than 50 SNPs revealed genomic regions that resulted in depression of up to 12.5 d and 260 L for calving interval and milk yield, respectively, when completely homozygous. Conclusions Genomic measures can be used instead of pedigree-based inbreeding to estimate inbreeding depression. Both the diagonal elements of the genomic relationship matrix and the proportion of homozygous SNPs can be used to measure inbreeding. Longer ROH (>3 Mb) were found to be associated with a reduction in milk yield and captured recent inbreeding independently and in addition to overall homozygosity. Inbreeding depression can be reduced by minimizing overall inbreeding but maybe also by avoiding the production of offspring that are homozygous for deleterious alleles at specific genomic regions that are associated with inbreeding depression.

Bosse M, Megens HJ, Madsen O, Crooijmans RP, Ryder OA, Austerlitz F, Groenen MA, de Cara MA . Using genome-wide measures of coancestry to maintain diversity and fitness in endangered and domestic pig populations
Genome Res, 2015,25(7):970-981.
URL [本文引用: 1]

de Cara Má, Villanueva B, Toro Má, Fernández J . Using genomic tools to maintain diversity and fitness in conservation programmes
Mol Ecol, 2013,22(24):6091-6099.
URLPMID:24128280 [本文引用: 1]
Conservation programmes aim at maximizing the survival probability of populations, by minimizing the loss of genetic diversity, which allows populations to adapt to changes, and controlling inbreeding increases. The best known strategy to achieve these goals is optimizing the contributions of the parents to minimize global coancestry in their offspring. Results on neutral scenarios showed that management based on molecular coancestry could maintain more diversity than management based on genealogical coancestry when a large number of markers were available. However, if the population has deleterious mutations, managing using optimal contributions can lead to a decrease in fitness, especially using molecular coancestry, because both beneficial and harmful alleles are maintained, compromising the long-term viability of the population. We introduce here two strategies to avoid this problem: The first one uses molecular coancestry calculated removing markers with low minor allele frequencies, as they could be linked to selected loci. The second one uses a coancestry based on segments of identity by descent, which measures the proportion of genome segments shared by two individuals because of a common ancestor. We compare these strategies under two contrasting mutational models of fitness effects, one assuming many mutations of small effect and another with few mutations of large effect. Using markers at intermediate frequencies maintains a larger fitness than using all markers, but leads to maintaining less diversity. Using the segment-based coancestry provides a compromise solution between maintaining diversity and fitness, especially when the population has some inbreeding load.

Joller S, Bertschinger F, Kump E, Spiri A, von Rotz A, Schweizer-Gorgas D, Drögemüller C, Flury C . Crossed beaks in a local Swiss chicken breed
BMC Vet Res, 2018, 14(1):68.
URL [本文引用: 1]
Crossed beaks have been reported to occur in Appenzeller Barthuhn, a local Swiss chicken breed. The assumed causes for this beak deformity which are also seen in other bird species including domestic chickens, range from environmental influences to genetic factors. The aim of this project was to characterize the prevalence, the phenotype, and the underlying genetics of crossed beaks in Appenzeller Barthuhn chickens. The estimated prevalence of 7% crossed beaks in Appenzeller Barthuhn was significantly higher compared to two other local Swiss chicken breeds. A breeding trial showed significantly higher prevalence of offspring with deformed beaks from mating of affected parents compared to mating of non-affected parents. Examination of 77 Appenzeller Barthuhn chickens with crossed beaks showed a variable phenotype presentation. The deviation of the beak from the median plane through the head ranged from 1掳 to 61 . In more than 60% of the cases, the upper and lower beak were bent in the same direction, whereas the remaining cases showed different forms of crossed beaks. Computed tomographic scans and bone maceration of the head of two chickens with crossed beaks revealed that the maxilla and the mandibula were affected, while other parts of the skull appeared to be normal. The gene LOC426217, a member of the keratin family, was postulated as a candidate gene for beak deformity in domestic chickens. Sequencing of the coding region revealed two significantly associated synonymous variants for crossed beaks in Appenzeller Barthuhn chickens. A genome-wide association study and a comparative analysis of runs of homozygosity based on high-density SNP array genotyping data of 53 cases and 102 controls showed no evidence of association. The findings suggest a hereditary cause of crossed beaks in Appenzeller Barthuhn chickens. However, the observed variation in the phenotype, together with the inconclusive molecular genetic results indicates the need for additional research to unravel the genetic architecture of this beak deformity.

Li MZ, Zhao YF, Ren J, Jiang SW, Li H . Opportunities and challenges of genetic and breeding research on the livestock in the age of '-omics'
Hereditas(Beijing), 2017,39(11):955-957.
URL [本文引用: 1]
高通量测序技术的飞速发展开启了生命科学领域组学时代的篇章。人类ENCODE、Roadmap、FANTOM等计划的逐步实施,进一步加深了人们对疾病产生分子机制的理解。2015年,动物基因组功能注解(Functional Annotation of Animal Genomes,FAANG)计划正式启动,其主要目标是全面而完善地注解家养动物基因组中的功能元件。该项目的启动凸显了农业动物领域相关研究的重要性,主要表现在:首先,农业动物基因组研究有利于揭示动物的进化、环境适应以及遗传选择;其次,以猪、羊
李明洲, 赵要风, 任军, 蒋思文, 李辉 . 组学时代农业动物遗传育种研究的机遇与挑战
遗传, 2017,39(11):955-957.
URL [本文引用: 1]
高通量测序技术的飞速发展开启了生命科学领域组学时代的篇章。人类ENCODE、Roadmap、FANTOM等计划的逐步实施,进一步加深了人们对疾病产生分子机制的理解。2015年,动物基因组功能注解(Functional Annotation of Animal Genomes,FAANG)计划正式启动,其主要目标是全面而完善地注解家养动物基因组中的功能元件。该项目的启动凸显了农业动物领域相关研究的重要性,主要表现在:首先,农业动物基因组研究有利于揭示动物的进化、环境适应以及遗传选择;其次,以猪、羊

Liang SY, Zhou ZK, Hou SS . The research progress of farm animal genomics based on sequencing technologies
Hereditas(Beiijng), 2017,39(4):276-292.
URL [本文引用: 1]
人类通过数千年的驯化和近代以来有计划性的育种,形成了当今多样化的畜禽品种,从而提供丰富的动物源性蛋白满足人类需求。在过去的100年里,数量遗传学应用于动物育种领域引发了畜禽育种技术的革命,但畜禽机体遗传发育体系相当复杂,一些性状仍然难以通过基于系谱的育种值进行高效选育,遗传潜能尚未充分发掘。人类基因组计划带来的理念和技术极大促进了畜禽基因组学的发展,使得人们可以从全基因组水平精准定位功能变异,挖掘功能元件的生物学意义,为畜禽分子设计育种提供重要的理论基础。本文对近10年来猪（Sus scrofa）、牛（Bos taurus）、牦牛（Bos grunniens）、山羊（Capra hircus）、绵羊（Ovis aries）、鸡（Gallus gallus）、鸭（Anas platyrhynchos）和鹅（Anser cygnoides）等主要畜禽的基因组学研究进展进行综述,分别从参考基因组构建和群体基因组学分析两个方面进行论述,并对畜禽基因组未来的研究工作进行了展望。
梁素芸, 周正奎, 侯水生 . 基于测序技术的畜禽基因组学研究进展
遗传, 2017,39(4):276-292.
URL [本文引用: 1]
人类通过数千年的驯化和近代以来有计划性的育种,形成了当今多样化的畜禽品种,从而提供丰富的动物源性蛋白满足人类需求。在过去的100年里,数量遗传学应用于动物育种领域引发了畜禽育种技术的革命,但畜禽机体遗传发育体系相当复杂,一些性状仍然难以通过基于系谱的育种值进行高效选育,遗传潜能尚未充分发掘。人类基因组计划带来的理念和技术极大促进了畜禽基因组学的发展,使得人们可以从全基因组水平精准定位功能变异,挖掘功能元件的生物学意义,为畜禽分子设计育种提供重要的理论基础。本文对近10年来猪（Sus scrofa）、牛（Bos taurus）、牦牛（Bos grunniens）、山羊（Capra hircus）、绵羊（Ovis aries）、鸡（Gallus gallus）、鸭（Anas platyrhynchos）和鹅（Anser cygnoides）等主要畜禽的基因组学研究进展进行综述,分别从参考基因组构建和群体基因组学分析两个方面进行论述,并对畜禽基因组未来的研究工作进行了展望。
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